CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. Figure 1. Percent of Adult Subjects with Active Psoriatic Arthritis Achieving ACR20 Responses in Trial PsA-1 through Week 24. 14.1 Clinical Trials in Subjects with Moderate-to-Severe Plaque Psoriasis. Adults with Moderate-to-Severe Plaque PsoriasisFour multicenter, randomized, double-blind trials [PsO-1 (NCT02684370), PsO-2 (NCT02684357), PsO-3 (NCT02672852), and PsO-4 (NCT02694523)] enrolled 2,109 subjects 18 years of age and older with moderate-to-severe plaque psoriasis who had body surface area (BSA) involvement of >=10%, static Physicians Global Assessment (sPGA) score of >=3 (moderate) in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on severity scale of to 4, and Psoriasis Area and Severity Index (PASI) score >=12. Overall, subjects had median baseline PASI score of 17.8 and median BSA of 20%. Baseline sPGA score was (severe) in 19% of subjects. total of 10% of trial subjects had history of diagnosed psoriatic arthritis. Across all trials, 38% of subjects had received prior phototherapy, 48% had received prior non-biologic systemic therapy, and 42% had received prior biologic therapy for the treatment of psoriasis. Trials PsO-1 and PsO-2In trials PsO-1 and PsO-2, 997 subjects were enrolled (including 598 subjects randomized to the SKYRIZI 150 mg group, 200 subjects randomized to the placebo group, and 199 to the biologic active control group). Subjects received treatment at Weeks 0, 4, and every 12 weeks thereafter. Both trials assessed the responses at Week 16 compared with placebo for the two co-primary endpoints: the proportion of subjects who achieved an sPGA score of (clear) or (almost clear) the proportion of subjects who achieved at least 90% reduction from baseline PASI (PASI 90)Secondary endpoints included the proportion of subjects who achieved PASI 100, sPGA 0, and Psoriasis Symptom Scale (PSS) at Week 16. The results are presented in Table 8. Table 8. Efficacy Results at Week 16 in Adults with Moderate-to-Severe Plaque Psoriasis in PsO-1 and PsO-2 PsO-1PsO-2 SKYRIZI(N=304)n (%)Placebo(N=102)n (%)SKYRIZI(N=294)n (%)Placebo(N=98)n (%)sPGA or (clear or almost clear)a267 (88)8 (8)246 (84)5 (5)PASI 90a229 (75)5 (5)220 (75)2 (2)sPGA (clear)112 (37)2 (2)150 (51)3 (3)PASI 100109 (36)0 (0)149 (51)2 (2)a Co-primary endpoints Examination of age, gender, race, body weight, baseline PASI score and previous treatment with systemic or biologic agents did not identify differences in response to SKYRIZI among these subgroups at Week 16. In PsO-1 and PsO-2 at Week 52, subjects receiving SKYRIZI achieved sPGA (58% and 60%, respectively), PASI 90 (82% and 81%, respectively), and PASI 100 (56% and 60%, respectively). Patient Reported OutcomesImprovements in signs and symptoms related to pain, redness, itching and burning at Week 16 compared to placebo were observed in both trials as assessed by the PSS. In PsO-1 and PsO-2, about 30% of the subjects who received SKYRIZI achieved PSS (none) at Week 16 compared to 1% of the subjects who received placebo. Trial PsO-3Trial PsO-3 enrolled 507 subjects (407 randomized to SKYRIZI 150 mg and 100 to placebo). Subjects received treatment at Weeks 0, 4, and every 12 weeks thereafter. At Week 16, SKYRIZI was superior to placebo on the co-primary endpoints of sPGA or (84% SKYRIZI and 7% placebo) and PASI 90 (73% SKYRIZI and 2% placebo). The respective response rates for SKYRIZI and placebo at Week 16 were: sPGA (46% SKYRIZI and 1% placebo); PASI 100 (47% SKYRIZI and 1% placebo); and PASI 75 (89% SKYRIZI and 8% placebo). Maintenance and Durability of ResponseIn PsO-1 and PsO-2, among the subjects who received SKYRIZI and had PASI 100 at Week 16, 80% (206/258) of the subjects who continued on SKYRIZI had PASI 100 at Week 52. For PASI 90 responders at Week 16, 88% (398/450) of the subjects had PASI 90 at Week 52. In PsO-3, subjects who were originally on SKYRIZI and had sPGA or at Week 28 were re-randomized to continue SKYRIZI every 12 weeks or withdrawal of therapy. At Week 52, 87% (97/111) of the subjects re-randomized to continue treatment with SKYRIZI had sPGA or compared to 61% (138/225) who were re-randomized to withdrawal of SKYRIZI. Moderate-to-Severe Plaque Psoriasis of the Scalp or Genital Area (Trial PsO-5)The efficacy of SKYRIZI was assessed in multicenter, randomized, double-blind, placebo-controlled trial [PsO-5 (NCT05969223)] that enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis of the scalp (Trial S), defined as Psoriasis Scalp Severity Index (PSSI) >=12, scalp Investigator Global Assessment (scalp IGA) >=3 (moderate), and >=30% of the scalp affected, or moderate-to-severe plaque psoriasis of the genital area (Trial G), defined as static Physicians Global Assessment of Genitalia (sPGA-G) >=3 (moderate) at baseline. All subjects had BSA >=1% and sPGA >=3 (moderate) at baseline.In trial PsO-5, subjects were randomized to receive either SKYRIZI 150 mg or placebo subcutaneously at Weeks and 4. Starting at Week 16, all subjects received SKYRIZI 150 mg every 12 weeks until the last dose at Week 40. Plaque Psoriasis of the Scalp PsO-5 Trial enrolled 105 subjects with moderate-to-severe plaque psoriasis of the scalp. The median age of enrolled subjects at baseline was 44 years (range 20 to 83 years) and 10% of the subjects were 65 years of age and older. Fifty-six (56)% of the subjects were male, 83% were White, 8% were Black or African American, and 5% were Asian; for ethnicity, 36% of the subjects identified as Hispanic or Latino. At baseline, 74% of the subjects had moderate plaque psoriasis of the scalp (scalp IGA of 3) and 26% had severe plaque psoriasis of the scalp (scalp IGA of 4). Median baseline PSSI was 32. Baseline BSA involvement was >=10% for 62% of the subjects and <10% for the remaining subjects. Median baseline BSA involvement was 11%. Baseline sPGA score was (severe) in 24% of the subjects.At baseline, 54% of subjects were naive to both non-biologic systemic and biologic therapy, 0% of subjects had received prior phototherapy, 15% had received prior non-biologic systemic therapy, and 37% had received prior biologic therapy. The results are presented in Table 9. Table 9. Efficacy Results at Week 16 in Adults with Moderate-to-Severe Psoriasis of the Scalp in PsO-5 Trial SEndpointSKYRIZI(N=51)n (%)Placebo(N=54)n (%)Treatment Difference (95% CI)scalp IGA of or (clear or almost clear)a31 (61)7 (13)47(31, 63)PSSI 90b27 (53)7 (13)40(24, 55)PSSI 100c23 (45)7 (13)31(15, 47)a Primary endpoint Achievement of >=90% improvement from baseline in PSSI Achievement of 100% improvement from baseline in PSSIPlaque Psoriasis of the Genital Area PsO-5 Trial enrolled 109 subjects with moderate-to-severe plaque psoriasis of the genital area. The median age of enrolled subjects at baseline was 45 years (range 19 to 77 years) and 15% of the subjects were 65 years of age and older. Sixty-five (65)% of the subjects were male, 90% were White, 4% were Asian, and 2% were Black or African American; for ethnicity, 29% of the subjects identified as Hispanic or Latino. At baseline, 62% of the subjects had moderate plaque psoriasis of the genital area (sPGA-G of 3) and 38% had severe or very severe plaque psoriasis of the genital area (sPGA-G of or 5). Baseline BSA involvement was >=10% for 63% of the subjects and <10% for the remaining subjects. Median baseline BSA involvement was 11%. Baseline sPGA score was (severe) in 19% of the subjects.At baseline, 61% of subjects were naive to both non-biologic systemic and biologic therapy, 3% of subjects had received prior phototherapy, 17% had received prior non-biologic systemic therapy, and 26% had received prior biologic therapy. The results are presented in Table 10.Table 10. Efficacy Results at Week 16 in Adults with Moderate-to-Severe Psoriasis of the Genital Area in PsO-5 Trial GEndpointSKYRIZI(N=55)n (%)Placebo(N=54)n (%)Treatment Difference (95% CI)sPGA-G of or (clear or minimal)a38 (69)7 (13)57(42, 72)sPGA-G of (clear)28 (51)3 (6)47(33, 61)GPI-NRS reduction of >=4-point from baselinebN=4120 (49)N=453 (7)43(27, 59)GenPs-SFQ text score of (never) or (rarely)c,dN=3122 (71)N=327 (22)46(27, 66)a Primary endpoint Improvement of genital itch severity as measured by reduction of at least points in the 11-point Genital Psoriasis Itch (GPI) Numeric Rating Scale (NRS) from the Genital Psoriasis Symptom Scale (GPSS) among subjects with baseline score >=4 Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ) Item (In the past week, how often did your genital psoriasis limit the frequency of your sexual activity) score ranges from to (0 never, = rarely, = sometimes, = often, = always); where higher scores indicate greater limitations on the frequency of sexual activity in the past week Among subjects with baseline score >=2Pediatric Subjects with Moderate-to-Severe Plaque Psoriasis The safety and efficacy of SKYRIZI were assessed in four-part trial [PsO-6 (NCT04435600)] [see Use in Specific Populations 8.4 ]. The trial included randomized, efficacy assessor-blinded, active treatment-controlled cohort of 82 pediatric subjects 12 years of age and older with moderate-to-severe plaque psoriasis defined as BSA involvement of >=10% with sPGA score of >=3 or PASI score >=12. Subjects were randomized 2:1 to receive SKYRIZI (N 54) or ustekinumab (N 28). Subjects weighing 40 kg or greater received SKYRIZI 150 mg and subjects weighing less than 40 kg received SKYRIZI 55 mg at Week 0, Week 4, and every 12 weeks thereafter. Fifty-six (56)% of subjects were female, 83% were White, 10% were Asian, and 5% were Black or African American; for ethnicity, 17% of subjects identified as Hispanic or Latino. At baseline, 82% of subjects had sPGA score of (moderate) and 9% of subjects had sPGA score of (severe). Subjects had median baseline PASI score of 15.7, and median baseline BSA of 18%. total of 4% of subjects had received prior biologic therapy.The co-primary endpoints were sPGA score of (clear) or (almost clear) and at least 2-point improvement from baseline, and PASI 75 at Week 16. The duration of treatment was up to 68 weeks.The efficacy results are presented below (see Table 11).Table 11. Efficacy Results at Week 16 in Pediatric Subjects 12 Years of Age and Older with Moderate-to-Severe Plaque Psoriasis in PsO-6SKYRIZI(N 54)n (%)sPGA or (clear or almost clear)a,b37 (69)PASI 75a 46 (85)PASI 90 35 (65)PASI 100 22 (41)sPGA (clear)22 (41)aco-primary endpointsband at least 2-point improvement from baseline at Week 16Maintenance of Response Subjects originally treated with SKYRIZI who achieved sPGA of or at Week 16 were re-randomized to continue SKYRIZI every 12 weeks through Week 52 or were withdrawn from treatment. For subjects who were re-randomized and also had at least 2-point improvement in sPGA from baseline at Week 16, 95% (18/19) of the subjects continuing SKYRIZI had sPGA of or and at least 2-point improvement from baseline at Week 52 compared with 39% (7/18) for those withdrawn from SKYRIZI.. the proportion of subjects who achieved an sPGA score of (clear) or (almost clear) the proportion of subjects who achieved at least 90% reduction from baseline PASI (PASI 90). 14.2 Clinical Trials in Adults with Active Psoriatic Arthritis. The safety and efficacy of SKYRIZI were assessed in 1407 subjects in randomized, double-blind, placebo-controlled trials (964 in PsA-1 [NCT03675308] and 443 in PsA-2 [NCT03671148]) in subjects 18 years and older with active psoriatic arthritis (PsA).Subjects in these trials had diagnosis of PsA for at least months based on the Classification Criteria for Psoriatic Arthritis (CASPAR), median duration of PsA of 4.9 years at baseline, >= tender joints and >=5 swollen joints, and active plaque psoriasis or psoriatic nail disease at baseline. Regarding baseline clinical presentation, 55.9% of subjects had >=3% BSA with active plaque psoriasis; 63.4% and 27.9% of subjects had enthesitis and dactylitis, respectively. In PsA-1 where psoriatic nail disease was further assessed, 67.3% had psoriatic nail disease.In PsA-1, all subjects had previous inadequate response or intolerance to non-biologic DMARD therapy and were biologic naive. In PsA-2, 53.5% of subjects had previous inadequate response or intolerance to non-biologic DMARD therapy, and 46.5% of subjects had previous inadequate response or intolerance to biologic therapy. In both trials, subjects were randomized to receive SKYRIZI 150 mg or placebo at Weeks 0, 4, and 16. Starting from Week 28, all subjects received SKYRIZI every 12 weeks. Both trials included long-term extension for up to an additional 204 weeks. Regarding use of concomitant medications, 59.6% of subjects were receiving concomitant methotrexate (MTX), 11.6% were receiving concomitant non-biologic DMARDs other than MTX, and 28.9% were receiving SKYRIZI monotherapy. For both trials, the primary endpoint was the proportion of subjects who achieved an American College of Rheumatology (ACR) 20 response at Week 24. Clinical Response In both trials, treatment with SKYRIZI resulted in significant improvement in measures of disease activity compared with placebo at Week 24. See Tables 12 and 13 for key efficacy results.In both trials, similar responses were seen regardless of concomitant non-biologic DMARD use, number of prior non-biologic DMARDs, age, gender, race, and BMI. In PsA-2, responses were seen regardless of prior biologic therapy.Table 12. Efficacy Results at Week 16 and Week 24 in Adults with Active Psoriatic Arthritis in Trial PsA-1EndpointPlaceboN=481Response Rate SKYRIZI N=483Response Rate Difference from Placebo (95% CI)ACR20 Response Week 16 33.4%56.3%a 23.1% (16.8, 29.4) Week 24 33.5%57.3%a 24% (18, 30)ACR50 Response Week 1611.1%26.4% 15.4% (10.6, 20.2) Week 2411.3%33.4 %22.2% (17.3, 27.2)ACR70 Response Week 162.7%11.8% 9.2% (6.1, 12.4) Week 244.7%15.3% 10.5% (6.9, 14.2)a. multiplicity-controlled p<=0.001, SKYRIZI vs. placebo comparison.A Subject was considered as non-responder after initiation of rescue medication or concomitant medications for PsA that could meaningfully impact efficacy assessment. Table 13. Efficacy Results at Week 16 and Week 24 in Adults with Active Psoriatic Arthritis in Trial PsA-2EndpointPlaceboN=219Response RateSKYRIZI N=224Response RateDifference from Placebo (95% CI)ACR20 Response Week 16 25.3% 48.3% 22.6% (13.9, 31.2) Week 24 26.5% 51.3% 24.5% (15.9, 33)ACR50 Response Week 166.8%20.3%13.5% (7.3, 19.7) Week 249.3%26.3%16.6% (9.7, 23.6)ACR70 Response Week 163.4%11.2%7.8% (3, 12.6) Week 245.9%12%6% (0.8, 11.3)a. multiplicity-controlled p<=0.001, SKYRIZI vs. placebo comparison. Subject was considered as non-responder after initiation of rescue medication or concomitant medications for PsA that could meaningfully impact efficacy assessment. The percent of subjects achieving ACR20 responses in trial PsA-1 through Week 24 is shown in Figure 1.Figure 1. Percent of Adult Subjects with Active Psoriatic Arthritis Achieving ACR20 Responses in Trial PsA-1 through Week 24The results of the components of the ACR response criteria for both trials are shown in Table 14. Table 14. Mean Change from Baseline in ACR ComponentsPsA-1 PsA-2 Placebo(N=481) Mean (SD)SKYRIZI (N=483) Mean (SD)Placebo(N=219) Mean (SD)SKYRIZI (N=224) Mean (SD) Number of Swollen Joints (0-66) Baseline12.2 (8)12.1 (7.8)13.6 (9)13 (8.7) Mean change at Week 16-5.5 (7)-7.7 (7.2)-5.4 (8.5)-8 (7.4) Mean change at Week 24-6.7 (7.2)-8.7 (7.2)-6.5 (7.8)-9.1 (7.6) Number of Tender Joints (0-68) Baseline20.5 (12.8)20.8 (14)22.3 (13.8)22.8 (14.9) Mean change at Week 16-6.3 (11.1)-10.7 (11.4) -6 (13.1)-11.3 (13) Mean change at Week 24-7.9 (10.7)-12 (12.3) -8.3 (11.3)-13 (12.5) Patients Assessment of Paina Baseline57.1 (22.6)57.1 (22.6)57 (23.1)55 (23.5) Mean change at Week 16-8.6 (23.7)-18.4 (26.3) -5.7 (22.7)-14.4 (26.4) Mean change at Week 24-10.9 (25.4)-21.4 (26.5) -8.7 (25.3)-15.3 (26.5) Patients Global Assessmenta Baseline57.4 (22.1)57.9 (21.7)56.2 (23)56.2 (21.8) Mean change at Week 16-10.2 (23.9)-19.4 (25.7) -4.9 (23.6)-17 (27.1) Mean change at Week 24-11.1 (25.1)-22.6 (26.9) -8.7 (25.4)-17.7 (27.7) Physician Global Assessmenta Baseline62.4 (17)61.3 (17.6)60.7 (16.4)63 (17) Mean change at Week 16-18.3 (22.5)-31.1 (23.4) -19 (23.3)-32.7 (24.7) Mean change at Week 24-22.2 (22.8)-34.8 (23.2) -21.3 (25.2)-35.5 (25.6) Health Assessment Questionnaire Disability Index (HAQ-DI)b Baseline1.2 (0.7)1.2 (0.7)1.1 (0.6)1.1 (0.6) Mean change at Week 16-0.1 (0.5)-0.3 (0.5) -0.1 (0.5)-0.2 (0.5) Mean change at Week 24-0.1 (0.5)-0.3 (0.5) -0.1 (0.4)-0.2 (0.5) High sensitivity C-reactive protein (hs-CRP) mg/L Baseline11.3 (14.1)11.9 (15.9)8.2 (17.1)7.4 (10.9) Mean change at Week 16-0.3 (14.7)-4.8 (14.2) -0.1 (6.8)-2.1 (7.5) Mean change at Week 24-0.2 (11.7)-4.3 (12.8) -0.5 (14.5)-1.8 (13.4)SD= Standard Deviation.a. Assessment based on Visual Analog Scale (100 mm) with the left end indicating no pain (for patients assessment of pain), very well (for patient global assessment), or no arthritis activity (for physician global assessment) and the right end indicating the worst possible pain (for patient assessment of pain), poor (for patient global assessment), or extremely active arthritis (for physician global assessment).b. Disability Index of the Health Assessment Questionnaire; = no difficulty to = inability to perform, measures the patients ability to perform the following: dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living.Treatment with SKYRIZI resulted in improvement in dactylitis and enthesitis in subjects with pre-existing dactylitis or enthesitis.In patients with coexistent plaque psoriasis receiving SKYRIZI, the skin lesions of psoriasis improved with treatment, relative to placebo, as measured by the Psoriasis Area Severity Index (PASI 90) at Week 24.Physical Function In both trials, patients treated with SKYRIZI showed statistically significant improvement from baseline in physical function compared with placebo as assessed by HAQ-DI at Week 24 (Table 14). The mean difference (95% CI) from placebo in HAQ-DI change from baseline at Week 24 was -0.20 (-0.26, -0.14) in trial PsA-1 and -0.16 (-0.26, -0.07) in trial PsA-2.In both trials, greater proportion of subjects achieved reduction of at least 0.35 in HAQ-DI score from baseline in the SKYRIZI group compared with placebo at Week 24. Other Health Related OutcomesIn both trials, general health status was assessed by the 36-Item Short Form Health Survey (SF-36 V2). Fatigue was assessed by Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue). In both trials at Week 24, subjects treated with SKYRIZI showed improvements in the SF-36 physical component summary scores compared with subjects who received placebo. There were also numerical improvements in subjects treated with SKYRIZI in physical functioning, role physical, bodily pain, general health, vitality, social functioning, mental health, role emotional domain scores and mental component summary scores in both trials at week 24 compared to placebo. In both trials at Week 24, subjects treated with SKYRIZI showed improvements in FACIT-Fatigue scores compared with subjects who received placebo.. 14.3 Clinical Trials in Subjects with Moderately to Severely Active Crohns Disease. Induction Trials (Trials CD-1 and CD-2)In two 12-week induction trials (CD-1; NCT03105128 and CD-2; NCT03104413), subjects with moderately to severely active Crohns disease were randomized to receive SKYRIZI 600 mg, SKYRIZI 1,200 mg, or placebo as an intravenous infusion at Week 0, Week 4, and Week 8. Moderately to severely active CD was defined as Crohns Disease Activity Index (CDAI) of 220 to 450 and Simple Endoscopic Score for Crohns disease (SES-CD) >=6 (or >=4 for isolated ileal disease). Subjects with inadequate response, loss of response, or intolerance to oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapy were enrolled. At baseline, the median CDAI was 307 (range: 76 634) and 307 (range: 72 651), and the median SES-CD was 12 (range: - 45) and 13 (range - 40), in CD-1 and CD-2, respectively. In CD-1, 58% (491/850) of subjects had failed or were intolerant to treatment with one or more biologic therapies (prior biologic failure). All subjects in CD-2 had prior biologic failure. At baseline, 30% and 34% of patients were receiving corticosteroids, 24% and 23% of patients were receiving immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), and 31% and 19% of patients were receiving aminosalicylates in CD-1 and CD-2, respectively. In CD-1 and CD-2 combined, the median age was 36 years (ranging from 16 to 80 years), 81% (1145/1419) of subjects were white, and 53% (753/1419) were male.In CD-1 and CD-2, the co-primary endpoints were clinical remission and endoscopic response at Week 12. Secondary endpoints included clinical response and endoscopic remission (see Table 15 and Table 16). The SKYRIZI 1,200 mg dosage did not demonstrate additional treatment benefit over the 600 mg dosage and is not recommended regimen [see Dosage and Administration 2.6 )].Table 15. Proportion of Subjects with Moderately to Severely Active Crohns Disease Meeting Efficacy Endpoints at Week 12 Trial CD-1 EndpointPlacebo SKYRIZI600 mg Intravenous InfusionaTreatmentDifferenceb(95% CI)Clinical Remissionc,dTotal PopulationN=17525%N=33645%21%e (12%, 29%)Prior biologic failuref N=9726% N=19542% Without prior biologic failureN=7823% N=14149% Endoscopic Responsec,gTotal PopulationN=17512%N=33640%28%e (21%, 35%) Prior biologic failuref N=9711%N=19533% Without prior biologic failureN=7813%N=14150%Clinical ResponsehTotal PopulationN=17537%N=33660%23%e (14%, 32%) Prior biologic failuref N=9734%N=19558% Without prior biologic failureN=78 40%N=14162%Endoscopic RemissioniTotal PopulationN=1759%N=33624%15%e (9%, 21%) Prior biologic failuref N=975%N=19518% Without prior biologic failureN=7814%N=14132%a. SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8b. Adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factors c. Co-primary endpointsd. CDAI <150e. <0.001f. Prior biologic failure includes inadequate response, loss of response, or intolerance to one or more biologic treatments for CDg. decrease in SES-CD 50% from baseline, or decrease of at least points for subjects with baseline score of and isolated ileal disease, based on central readingh. reduction of CDAI >= 100 points from baselinei. SES-CD <= and at least 2-point reduction from baseline, with no individual subscore greater than 1, based on central readingTable 16. Proportion of Subjects with Moderately to Severely Active Crohns Disease Meeting Efficacy Endpoints at Week 12 Trial CD-2a EndpointPlacebo N=187SKYRIZI600 mg Intravenous InfusionbN=191TreatmentDifferencec(95% CI)Clinical Remissiond,e20%42%22%f (13%, 31%)Endoscopic Responsed,g 11%29%18%f (10%, 25%)Clinical Responseh30%60%29%f (20%, 39%)Endoscopic Remissioni4%19%15%f (9%, 21%)a. All subjects enrolled in CD-2 had prior biologic failure. Prior biologic failure includes inadequate response, loss of response, or intolerance to one or more biologic treatments for CDb. SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8c. Adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomization stratification factorsd. Co-primary endpointse. CDAI score <150f. < 0.001g. decrease in SES-CD 50% from baseline, or decrease of at least points for subjects with baseline score of and isolated ileal disease, based on central readingh. reduction of CDAI >= 100 points from baselinei. SES-CD <= and at least 2-point reduction versus from baseline, with and no individual subscore greater than 1, based on central readingOnset of clinical response and clinical remission based on CDAI occurred as early as Week in greater proportion of subjects treated with the SKYRIZI 600 mg induction regimen compared to placebo.Reductions in stool frequency and abdominal pain were observed in greater proportion of subjects treated with the SKYRIZI 600 mg induction regimen compared to placebo at Week 12.Trial CD-3The maintenance trial CD-3 evaluated 382 subjects who achieved clinical response defined as reduction in CDAI of at least 100 points from baseline after 12 weeks of induction treatment with intravenous SKYRIZI in trials CD-1 and CD-2. Subjects were randomized to receive maintenance regimen of SKYRIZI 180 mg or SKYRIZI 360 mg or placebo at Week 12 and every weeks thereafter for up to an additional 52 weeks.The co-primary endpoints in CD-3 were clinical remission and endoscopic response at Week 52 (see Table 17). Table 17. Proportion of Subjects with Moderately to Severely Active Crohns Disease Meeting Efficacy Endpoints at Week 52 Trial CD-3EndpointPlaceboaSKYRIZI 180 mg Subcutaneous InjectionbSKYRIZI 360 mg Subcutaneous Injectionc Treatment Difference vs Placebod(95% CI)SKYRIZI180 mgSKYRIZI360 mgClinical Remissione,fTotal PopulationN=13046%N=13561%N=11757%17%g (6%, 28%)14%g (3%, 26%)Prior biologic failureh N=9940%N=9556%N=8351%Without prior biologic failureN=3165%N=4075%N=3471%Endoscopic Responsee,iTotal PopulationN=13022%N=13550%N=11748%30%g (20%, 39%)31%g (21%, 41%)Prior biologic failureh N=9921%N=9544%N=8344%Without prior biologic failureN=3123%N=4065%N=3459%a. The placebo group consisted of patients who were in response to SKYRIZI and were randomized to receive placebo at the start of maintenance therapy.b. SKYRIZI 180 mg at Week 12 and every weeks thereafter for up to an additional 52 weeksc. SKYRIZI 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeksd. Adjusted treatment difference and 95% CI computed using Cochran-Mantel-Haenszel method adjusted for randomization stratification factorse. Co-primary endpointsf. CDAI <150g. <0.05h. Prior biologic failure includes inadequate response, loss of response, or intolerance to one or more biologic treatments for CD i. decrease in SES-CD 50% from baseline, or decrease of at least points for subjects with baseline score of and isolated ileal disease, based on central readingEndoscopic remission was observed at Week 52 in 33% (44/135) of subjects treated with the SKYRIZI 180 mg maintenance regimen and 41% (48/117) of subjects treated with the SKYRIZI 360 mg maintenance regimen, compared to 13% (17/130) of subjects treated with placebo. This endpoint was not statistically significant under the prespecified multiple testing procedure.. 14.4 Clinical Trials in Subjects with Moderately to Severely Active Ulcerative Colitis. Induction Trial (Trial UC-1)In the 12-week induction trial (UC-1; NCT03398148), 966 subjects with moderately to severely active ulcerative colitis were randomized and received SKYRIZI 1,200 mg or placebo as an intravenous infusion at Week 0, Week 4, and Week 8. Disease activity was assessed by the modified Mayo score (mMS), 3-component Mayo score (0-9) which consists of the following subscores (0 to for each subscore): stool frequency (SFS), rectal bleeding (RBS), and findings on centrally read endoscopy score (ES). An ES of was defined by marked erythema, lack of vascular pattern, any friability, and/or erosions; an ES of was defined by spontaneous bleeding and ulceration. Enrolled subjects had mMS between and 9, with an ES of or 3. Subjects with inadequate response, or intolerance to oral aminosalicylates, corticosteroids, immunomodulators, biologics, Janus Kinase inhibitors (JAKi), and/or sphingosine-1-phosphate receptor modulators (S1PRM) were enrolled. At baseline in UC-1, the median mMS was 7; 37% had severely active disease (mMS >7); 69% had an ES of 3. In UC-1, 52% (499/966) of subjects had failed (inadequate response or intolerance) treatment with one or more biologics, JAKi or S1PRM. Of these 499 subjects, 484 (97%) failed biologics and 90 (18%) failed JAK inhibitors. Enrolled subjects were permitted to use stable dose of oral corticosteroids (up to 20 mg/day prednisone or equivalent), immunomodulators, and aminosalicylates. At baseline, 36% of subjects were receiving corticosteroids, 16% of subjects were receiving immunomodulators (including azathioprine, 6-mercaptopurine, methotrexate), and 73% of subjects were receiving aminosalicylates in UC-1.In UC-1, the primary endpoint was clinical remission defined using the mMS at Week 12 (see Table 18). Key secondary endpoints included clinical response, endoscopic improvement, and histologic endoscopic mucosal improvement (see Table 18).Table 18. Proportion of Subjects with Moderately to Severely Active Ulcerative Colitis Meeting Efficacy Endpoints at Week 12 Trial UC-1EndpointPlaceboSKYRIZI 1,200 mg Intravenous InfusionaTreatment Difference (95% CI)bClinical RemissioncTotal PopulationN=3208%N=64624%16%h (12%, 20%)Prior biologic, JAKi, or S1PRM failured N=1686%N=33114%Without prior biologic, JAKi, or S1PRM failureN=1529%N=31533%Clinical ResponseeTotal PopulationN=32036%N=64665%29%h (23%, 35%)Prior biologic, JAKi, or S1PRM failured N=16832%N=33156%Without prior biologic, JAKi, or S1PRM failureN=15241%N=31575%Endoscopic ImprovementfTotal PopulationN=32012%N=64636%25%h (20%, 30%)Prior biologic, JAKi, or S1PRM failured N=16810%N=33126%Without prior biologic, JAKi, or S1PRM failureN=15214%N=31547%Histologic Endoscopic Mucosal Improvement (HEMI)gTotal PopulationN=3207%N=64624%17%h (13%, 21%)Prior biologic, JAKi, or S1PRM failured N=1687%N=33116%Without prior biologic, JAKi, or S1PRM failureN=1528%N=31533%a SKYRIZI 1,200 mg as an intravenous infusion at Week 0, Week 4, and Week b Adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for stratification factors Per mMS: SFS <= and not greater than baseline, RBS 0, and ES <= without friability Prior failure includes inadequate response or intolerance to treatment with one or more of the following: biologic therapies, Janus Kinase inhibitors (JAKi), and/or sphingosine-1-phosphate receptor modulators (S1PRM) Per mMS: decrease >= points and >= 30% from baseline, and decrease in RBS >= from baseline or an absolute RBS <= f ES <= without the evidence of friability ES <= without the evidence of friability and Geboes score <= 3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction and no erosions, ulcerations or granulation tissue) p 0.001UC-1 was not designed to evaluate the relationship of histologic endoscopic mucosal improvement at week 12 to disease progression and long-term outcomes.Rectal Bleeding and Stool Frequency SubscoresDecreases in rectal bleeding and stool frequency subscores in subjects treated with SKYRIZI compared to placebo were observed as early as weeks.Endoscopic Assessment Endoscopic remission was defined as ES of 0. At Week 12, greater proportion of subjects treated with SKYRIZI compared to placebo achieved endoscopic remission (11% vs 3%). Bowel UrgencyA greater proportion of subjects treated with the SKYRIZI 1,200 mg induction regimen compared to placebo had no bowel urgency (44% vs 27%) at Week 12.FatigueIn UC-1, subjects treated with SKYRIZI experienced clinically meaningful improvement in fatigue, assessed by change from baseline in FACIT-F score, at Week 12, compared to placebo-treated subjects. The effect of SKYRIZI to improve fatigue after 12 weeks of induction has not been established.Other UC Symptoms The proportion of subjects who had no nocturnal bowel movements was greater in subjects treated with SKYRIZI compared to placebo at Week 12 (67% vs 43%).Maintenance Trial UC-2The maintenance trial (UC-2; NCT03398135) evaluated 547 subjects who received one of three SKYRIZI induction regimens, including the 1,200 mg regimen, for 12 weeks in Trials UC-1 or UC-3 and demonstrated clinical response per mMS after 12 weeks. Subjects were randomized to receive maintenance regimen of subcutaneous (SC) SKYRIZI 180 mg or SKYRIZI 360 mg or placebo at Week 12 and every weeks thereafter for up to an additional 52 weeks.In UC-2, 75% (411/547) of subjects had failed (inadequate response or intolerance) treatment with one or more biologics, JAKi, or S1PRM. Of these 411 subjects, 407 (99%) failed biologics and 78 (19%) failed JAK inhibitors. The primary endpoint in UC-2 was clinical remission using mMS at Week 52 (see Table 19). Key secondary endpoints included corticosteroid-free clinical remission, endoscopic improvement, and histologic endoscopic mucosal improvement (see Table 19).Table 19. Proportion of Subjects with Moderately to Severely Active Ulcerative Colitis Meeting Efficacy Endpoints at Week 52 Trial UC-2EndpointPlaceboaSKYRIZI 180 mg SC InjectionbSKYRIZI 360 mg SC InjectioncClinical remissiond Total PopulationN=18226%N=17945%N=18641%Treatment Difference vs Placeboe (95% CI)20% [11%, 29%]16% [7%, 25%]Prior biologic, JAKi, or S1PRM failuref N=13824%N=13441%N=13932%Without prior biologic, JAKi, or S1PRM failureN=4432%N=4558%N=4767%Corticosteroid-free clinical remissiong Total PopulationN=18226%N=17945%N=18640%Treatment Difference vs Placeboe (95% CI)20% [11%, 29%]16%j [7%, 25%] Prior biologic, JAKi, or S1PRM failuref N=13824%N=13440%N=13932%Without prior biologic, JAKi, or S1PRM failureN=4432%N=4558%N=4764%Endoscopic improvementh Total PopulationN=18231%N=17951%N=18648%Treatment Difference vs Placeboe (95% CI)20% [11%, 30%]18% [8%, 27%]Prior biologic, JAKi, or S1PRM failuref N=13830%N=13448%N=13939%Without prior biologic, JAKi, or S1PRM failureN=4434%N=4560%N=4776%Histologic Endoscopic Mucosal Improvementi Total PopulationN=18224%N=17943%N=18642%Treatment Difference vs Placeboe (95% CI)20% [11%, 29%]20% [11%, 29%]Prior biologic, JAKi, or S1PRM failuref N=13822%N=13439%N=13933%Without prior biologic, JAKi, or S1PRM failureN=4430%N=4555%N=4769%a The placebo group consisted of subjects who were in response to 12 weeks of SKYRIZI induction and were randomized to receive placebo at the start of maintenance therapy. SKYRIZI 180 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks SKYRIZI 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks Per mMS: SFS <= and not greater than baseline, RBS 0, and ES <= without friability Adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for stratification factors Prior failure includes inadequate response or intolerance to treatment with one or more of the following: biologic therapies, Janus Kinase inhibitors (JAKi), and/or sphingosine-1-phosphate receptor modulators (S1PRM) Clinical remission per mMS at Week 52 and corticosteroid-free for >=90 days ES <= without the evidence of friability ES <= 1without the evidence of friability and Geboes score <= 3.1 (indicating neutrophil infiltration in <5% of crypts, no crypt destruction and no erosions, ulcerations or granulation tissue) p 0.001Endoscopic Assessment Endoscopic remission was defined as ES of 0. In UC-2, greater proportion of subjects treated with SKYRIZI 180 mg and SKYRIZI 360 mg compared to placebo achieved endoscopic remission at Week 52 (23% and 24% vs 15%).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are discussed in other sections of labeling: Hypersensitivity Reactions [see Warnings and Precautions 5.1 )] Infections [see Warnings and Precautions 5.2 )] Tuberculosis [see Warnings and Precautions 5.3 )] Hepatotoxicity [see Warnings and Precautions 5.4 )] Hypersensitivity Reactions [see Warnings and Precautions 5.1 )] Infections [see Warnings and Precautions 5.2 )] Tuberculosis [see Warnings and Precautions 5.3 )] Hepatotoxicity [see Warnings and Precautions 5.4 )] Most common adverse reactions are:Plaque Psoriasis and Psoriatic Arthritis (>= 1%): upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections. (6.1) Crohns Disease (>3%): Induction: upper respiratory infections, headache, and arthralgia. (6.1) Maintenance: arthralgia, abdominal pain, injection site reactions, anemia, pyrexia, back pain, arthropathy, and urinary tract infection. (6.1) Ulcerative Colitis (>=3%): Induction: arthralgia. (6.1) Maintenance: arthralgia, pyrexia, injection site reactions, and rash. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. Plaque Psoriasis and Psoriatic Arthritis (>= 1%): upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections. (6.1) Crohns Disease (>3%): Induction: upper respiratory infections, headache, and arthralgia. (6.1) Maintenance: arthralgia, abdominal pain, injection site reactions, anemia, pyrexia, back pain, arthropathy, and urinary tract infection. (6.1) Ulcerative Colitis (>=3%): Induction: arthralgia. (6.1) Maintenance: arthralgia, pyrexia, injection site reactions, and rash. (6.1). 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical trials of drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Plaque PsoriasisA total of 2234 subjects were treated with SKYRIZI in clinical development trials in plaque psoriasis. Of these, 1208 subjects with psoriasis were exposed to SKYRIZI for at least one year. Data from placebo- and active-controlled trials were pooled to evaluate the safety of SKYRIZI for up to 16 weeks. In total, 1306 subjects were evaluated in the SKYRIZI 150 mg group. Table summarizes the adverse reactions that occurred at rate of at least 1% and at higher rate in the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials. Table 4. Adverse Reactions Occurring in >= 1% of Adults with Plaque Psoriasis on SKYRIZI through Week 16Adverse Drug ReactionsSKYRIZIN 1306n (%)PlaceboN 300n (%)Upper respiratory infectionsa 170 (13)29 (9.7)Headacheb 46 (3.5)6 (2) Fatiguec 33 (2.5)3 (1)Injection site reactionsd 19 (1.5)3 (1)Tinea infectionse 15 (1.1)1 (0.3)a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis Includes: headache, tension headache, sinus headache, cervicogenic headache Includes: fatigue, asthenia Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation, irritation, pain, pruritus, reaction, swelling, warmth Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection, onychomycosis Adverse reactions that occurred in 1% but 0.1% of subjects in the SKYRIZI group and at higher rate than in the placebo group through Week 16 were folliculitis and urticaria. Specific Adverse ReactionsInfections: In the first 16 weeks, infections occurred in 22.1% of the SKYRIZI group (90.8 events per 100 patient-years) compared with 14.7% of the placebo group (56.5 events per 100 patient-years) and did not lead to discontinuation of SKYRIZI. The rates of serious infections for the SKYRIZI group and the placebo group were <=0.4%. Serious infections in the SKYRIZI group included cellulitis, osteomyelitis, sepsis, and herpes zoster. In Trials PsO-1 and PsO-2, through Week 52, the rate of infections (73.9 events per 100 patient-years) was similar to the rate observed during the first 16 weeks of treatment. Safety Through Week 52Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were similar to those observed during the first 16 weeks of treatment. During this period, serious infections that led to trial discontinuation included pneumonia. Plaque Psoriasis of the Scalp or Genital AreaThe overall safety profile observed in clinical trials of subjects with moderate-to-severe plaque psoriasis of the scalp or genital area treated with SKYRIZI is generally consistent with the safety profile observed in previous clinical trials of subjects with moderate-to-severe plaque psoriasis [see Clinical Studies 14.1 )].Adverse Reactions in Pediatric Subjects Years of Age and Older with Plaque PsoriasisThe safety of SKYRIZI was evaluated in four-part trial that included 137 pediatric subjects years of age and older with moderate-to-severe plaque psoriasis [see Clinical Studies 14.1 )]. Overall, the safety profile observed in pediatric subjects years of age and older treated with SKYRIZI for up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.Adverse Reactions in Adult Subjects with Psoriatic ArthritisThe overall safety profile observed in adult subjects with psoriatic arthritis treated with SKYRIZI is generally consistent with the safety profile in adult subjects with plaque psoriasis. Additionally, in the Phase placebo-controlled trials the incidence of hepatic events was higher in the SKYRIZI group (5.4%, 16.7 events per 100 patient-years) compared to the placebo group (3.9%, 12.6 events per 100 patient-years). Of these, the most common events that were reported more frequently in both the placebo group and the SKYRIZI group were ALT increased (placebo: n=12 (1.7%); SKYRIZI: n=16 (2.3%)), AST increased (placebo: n=9 (1.3%); SKYRIZI: n=13 (1.8%)), and GGT increased (placebo: n=5 (0.7%); SKYRIZI: n=8 (1.1%)). There were no serious hepatic events reported. The incidence of hypersensitivity reactions was higher in the SKYRIZI group (n=16, 2.3%) compared to the placebo group (n=9, 1.3%). In the Phase placebo-controlled trials, hypersensitivity reactions reported at higher rate in the SKYRIZI group included rash (placebo: n=4 (0.6%); SKYRIZI: n=5 (0.7%)), allergic rhinitis (placebo: n=1 (0.1%); SKYRIZI: n=2 (0.3%)), and facial swelling (placebo: n=0 (0.0%); SKYRIZI n=1 (0.1%)). One case of anaphylaxis was reported in subject who received SKYRIZI in the Phase clinical trial.Adverse Reactions in Adult Subjects with Crohns Disease SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohns disease in two randomized, double-blind, placebo-controlled induction trials (CD-1, CD-2) and randomized, double-blind, placebo-controlled, dose-finding trial (CD-4; NCT02031276). Long-term safety up to 52 weeks was evaluated in subjects who responded to induction therapy in randomized, double-blind, placebo-controlled maintenance trial (CD-3) [see Clinical Studies 14.3 )]. In the two induction trials (CD-1, CD-2) and the dose finding trial (CD-4), 620 subjects received the SKYRIZI intravenous induction regimen at Weeks 0, and 8. In the maintenance trial (CD-3), 297 subjects who achieved clinical response, defined as reduction in CDAI of at least 100 points from baseline after 12 weeks of induction treatment with intravenous SKYRIZI in trials CD-1 and CD-2, received maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every weeks thereafter for up to an additional 52 weeks.Adverse reactions reported in 3% of subjects in induction trials and at higher rate than placebo are shown in Table 5.Table 5. Adverse Drug Reactions Reported in 3% of Subjects with Crohns Disease Treated with SKYRIZI in Placebo-Controlled 12-Week Induction Trials (CD-1, CD-2, and CD-4)Adverse Drug ReactionsSKYRIZI600 mg Intravenous InfusionaN 620n (%)PlaceboN 432n (%)Upper respiratory infectionsb 66 (10.6)40 (9.3)Headachec 41 (6.6)24 (5.6)Arthralgia31 (5)19 (4.4)a SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8. Includes: influenza like illness, nasopharyngitis, influenza, pharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, COVID-19, nasal congestion, respiratory tract infection viral, viral pharyngitis, tonsillitis, upper respiratory tract inflammation Includes: headache, tension headacheAdverse reactions reported in >3% of subjects in the maintenance trial and at higher rate than placebo are shown in Table 6.Table 6. Adverse Reactions Reported in >3% of Subjects with Crohns Disease Treated with SKYRIZIa in Placebo-Controlled 52-Week Maintenance Trial (CD-3) Adverse Drug ReactionsSKYRIZI180 mg Subcutaneous InjectionN 155n (%)SKYRIZI360 mg Subcutaneous InjectionN 142n (%)PlaceboN 143n (%)Arthralgia13 (8.4)13 (9.2)12 (8.4)Abdominal painb (5.8)12 (8.5)6 (4.2)Injection site reactionsc,d (4.5)8 (5.6)4 (2.8) Anemia7 (4.5)7 (4.9)6 (4.2)Pyrexia4 (2.6)7 (4.9)4 (2.8)Back pain (1.9)6 (4.2)3 (2.1)Arthropathy1 (0.6)5 (3.5)2 (1.4)Urinary tract infection1 (0.6)5 (3.5)4 (2.8)a SKYRIZI 180 mg or 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks Includes: abdominal pain, abdominal pain upper, abdominal pain lower Includes: injection site rash, injection site erythema, injection site swelling, injection site urticaria, injection site warmth, injection site pain, injection site hypersensitivity, injection site reaction Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject for the rate calculations. Specific Adverse ReactionsInfections: In the maintenance trial (CD-3) through Week 52, the rate of infections was 32.3% (50.2 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 36.6% (60.8 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 36.4% (60.3 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. The rate of serious infections was 2.6% (2.7 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 5.6% (7.4 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 2.1% (2.4 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. Lipid Elevations: Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol [LDL-C]) were first assessed at weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from baseline and increases relative to placebo were observed at Week and remained stable to Week 12. Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to mean absolute value of 175.1 mg/dL at Week 12. Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to mean absolute value of 92.6 mg/dL at Week 12. Mean LDL-C increased by 3.1 mg/dL from baseline to mean absolute value of 99 mg/dL at Week 52 with SKYRIZI 180 mg maintenance treatment and by 2.3 mg/dL from baseline to mean absolute value of 102.2 mg/dL at Week 52 with SKYRIZI 360 mg maintenance treatment (CD-3). Adverse Reactions in Adult Subjects with Ulcerative Colitis SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active ulcerative colitis in randomized, double-blind, placebo-controlled induction trial (UC-1) and randomized, double-blind, placebo-controlled, dose-finding trial (UC-3). Long-term safety up to 52 weeks was evaluated in subjects who responded to induction therapy in randomized, double-blind, placebo-controlled maintenance trial (UC-2) [see Clinical Studies 14.4 )]. In the induction trials (UC-1 and UC-3), 712 subjects received the SKYRIZI 1,200 mg intravenous induction regimen at Weeks 0, and 8. In the maintenance trial (UC-2), 347 subjects who achieved clinical response, defined as decrease in mMS of >=2 points and >=30% from baseline and decrease in RBS >=1 from baseline or an absolute RBS <=1, received maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every weeks thereafter for up to an additional 52 weeks.The adverse reaction reported in >=3% subjects treated with SKYRIZI in the ulcerative colitis induction trials (UC-1 and UC-3) and at higher rate than placebo was arthralgia (3% SKYRIZI vs 1% placebo). Adverse reactions reported in >=3% of subjects treated with SKYRIZI in the maintenance trial (UC-2) and at higher rate than placebo are shown in Table 7.Table 7. Adverse Reactions Reported in >=3% of Subjects with Ulcerative Colitis Treated with SKYRIZIa in Placebo-Controlled 52-Week Maintenance Trial (UC-2) Adverse Drug ReactionsSKYRIZI180 mg Subcutaneous InjectionN 170n (%)SKYRIZI360 mg Subcutaneous InjectionN 177n (%)PlaceboN 173n (%)Arthralgia9 (5.3)17 (9.6)8 (4.6)Pyrexia8 (4.7)7 (4)6 (3.5)Injection site reactionsb,c (2.9) (2.8) (1.2)Rashd (4.1) (0.6) (1.7)a SKYRIZI 180 mg or 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks Includes: application site pain, injection site erythema, injection site pain, injection site pruritus, injection site reaction Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject for the rate calculations. Includes: rash and rash macularSpecific Adverse ReactionsThe rates of infections, serious infections, and lipid elevations in subjects with UC who received SKYRIZI compared to subjects who received placebo in the induction trials (UC-1 and UC-3) and maintenance trial (UC-2) were similar to the rates in subjects with CD who received SKYRIZI compared to subjects who received placebo in the induction trials (CD-1, CD-2, and CD-4) and maintenance trial (CD-3). Infections: In the maintenance trial (CD-3) through Week 52, the rate of infections was 32.3% (50.2 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 36.6% (60.8 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 36.4% (60.3 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. The rate of serious infections was 2.6% (2.7 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 5.6% (7.4 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 2.1% (2.4 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. Lipid Elevations: Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol [LDL-C]) were first assessed at weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from baseline and increases relative to placebo were observed at Week and remained stable to Week 12. Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to mean absolute value of 175.1 mg/dL at Week 12. Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to mean absolute value of 92.6 mg/dL at Week 12. Mean LDL-C increased by 3.1 mg/dL from baseline to mean absolute value of 99 mg/dL at Week 52 with SKYRIZI 180 mg maintenance treatment and by 2.3 mg/dL from baseline to mean absolute value of 102.2 mg/dL at Week 52 with SKYRIZI 360 mg maintenance treatment (CD-3). 6.2 Postmarketing Experience. The following adverse reactions have been reported during post-approval of SKYRIZI. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to SKYRIZI exposure:Skin and subcutaneous tissue disorders: eczema and rash Skin and subcutaneous tissue disorders: eczema and rash.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenicity and mutagenicity studies have not been conducted with SKYRIZI. No effects on male fertility parameters were observed in sexually mature male cynomolgus monkeys dosed weekly for 26 weeks with 50 mg/kg risankizumab-rzaa at times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and 39 times the exposure in humans administered the maximum recommended maintenance dose (360 mg).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Risankizumab-rzaa is humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is naturally occurring cytokine that is involved in inflammatory and immune responses. Risankizumab-rzaa inhibits the release of pro-inflammatory cytokines and chemokines. 12.2 Pharmacodynamics. No formal pharmacodynamics studies have been conducted with risankizumab-rzaa. 12.3 Pharmacokinetics. Risankizumab-rzaa plasma concentrations, after single dose administration increased dose proportionally from 18 mg to 360 mg when administered subcutaneously (0.12 to 2.4 times the lowest recommended dose and 0.05 to times the highest recommended dose) and from 200 mg to 1,800 mg when administered as an up to 3-hour intravenous infusion (0.2 to times the recommended dose) in healthy subjects. In subjects with plaque psoriasis treated with 150 mg subcutaneously at Weeks 0, 4, and every 12 weeks thereafter, steady-state peak concentration (Cmax) and trough concentration (Ctrough) are estimated to be 12 mcg/mL and mcg/mL, respectively. With the same subcutaneous dosing regimen, the pharmacokinetics of risankizumab-rzaa in subjects with psoriatic arthritis were similar to that in subjects with plaque psoriasis.In subjects with Crohns disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48.In subjects with ulcerative colitis treated with 1,200 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every weeks thereafter, the median Cmax and Ctrough are estimated to be 350 and 87.7 mcg/mL, respectively, during the induction period (Weeks 8-12); and the steady state median Cmax and Ctrough are estimated to be 19.6 and 4.64 ug/mL, respectively, for 180 mg or 39.2 mcg/mL and 9.29 mcg/mL, respectively, for 360 mg, during the maintenance period (Weeks 40-48).Based on population pharmacokinetic analyses, the pharmacokinetics of risankizumab-rzaa in subjects with ulcerative colitis was generally similar to that in subjects with Crohns disease.AbsorptionThe absolute bioavailability of risankizumab-rzaa was estimated to be 74 to 89% following subcutaneous injection. In healthy subjects, following administration of single subcutaneous dose, Cmax was reached by to 14 days. DistributionThe estimated steady-state volume of distribution (inter-subject CV%) was 11.2 (34%) in subjects with plaque psoriasis, and 7.68 (64%) in subjects with Crohns disease. EliminationThe estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and 0.30 L/day (34%) and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohns disease, respectively. MetabolismThe metabolic pathway of risankizumab-rzaa has not been characterized. As humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in manner similar to endogenous IgG. Specific PopulationsPediatric PatientsPlaque Psoriasis: Risankizumab-rzaa exposures in pediatric subjects years of age and older with plaque psoriasis receiving weight-based dosing regimens were consistent with those in adults. At the recommended dosing regimens evaluated in these subjects, estimated median steady-state peak and trough plasma concentrations were 15.7 and 2.3 mcg/mL, respectively, in subjects weighing less than 40 kg, and 11.1 and 1.6 mcg/mL, respectively, in subjects weighing 40 kg or greater. Psoriatic Arthritis: Risankizumab exposures in patients years of age and older with active psoriatic arthritis at the recommended pediatric dosage are predicted to be comparable to those observed in adult patients with psoriatic arthritis based on population pharmacokinetic modeling simulation.Geriatric PatientsRisankizumab-rzaa exposures (Ctrough) in geriatric patients (>=65 years) are comparable to those in younger adult patients within each indication. No studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab-rzaa. Body WeightRisankizumab-rzaa clearance and volume of distribution increase and plasma concentrations decrease as body weight increases; however, no dose adjustment is recommended based on body weight in adult patients. Drug Interaction StudiesCytochrome P450 SubstratesNo clinically significant changes in exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate), or midazolam (CYP3A substrate) were observed when used concomitantly with risankizumab-rzaa in subjects with plaque psoriasis (risankizumab-rzaa 150 mg administered subcutaneously at Weeks 0, 4, 8, and 12) and subjects with Crohns disease or ulcerative colitis (risankizumab-rzaa 1,800 mg administered intravenously at Weeks 0, 4, and 8, i.e., times and 1.5 times the recommended dose for Crohns disease and ulcerative colitis, respectively). Plaque Psoriasis: Risankizumab-rzaa exposures in pediatric subjects years of age and older with plaque psoriasis receiving weight-based dosing regimens were consistent with those in adults. At the recommended dosing regimens evaluated in these subjects, estimated median steady-state peak and trough plasma concentrations were 15.7 and 2.3 mcg/mL, respectively, in subjects weighing less than 40 kg, and 11.1 and 1.6 mcg/mL, respectively, in subjects weighing 40 kg or greater. Psoriatic Arthritis: Risankizumab exposures in patients years of age and older with active psoriatic arthritis at the recommended pediatric dosage are predicted to be comparable to those observed in adult patients with psoriatic arthritis based on population pharmacokinetic modeling simulation.. 12.6 Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the trials described below with the incidence of ADA in other trials, including those of SKYRIZI or other risankizumab products. Moderate-to-Severe Plaque PsoriasisBy Week 52, approximately 24% (263/1079) of adults treated with SKYRIZI at the recommended dosage developed antibodies to risankizumab-rzaa. Of the subjects who developed antibodies to risankizumab-rzaa, approximately 57% (14% of all subjects treated with SKYRIZI) had antibodies that were classified as neutralizing. Higher antibody titers in approximately 1% of subjects treated with SKYRIZI were associated with lower risankizumab-rzaa concentrations and reduced clinical response. In pediatric subjects years of age and older, approximately 15% (13/88) of subjects treated with SKYRIZI at the recommended dose developed antibodies to risankizumab-rzaa by Week 52. Of the 13 subjects who developed antibodies to risankizumab-rzaa, approximately 15% (2.3% of all subjects treated with SKYRIZI) had antibodies that were classified as neutralizing. Due to the small number of subjects who developed antibodies to risankizumab-rzaa, it is difficult to determine the impact of the antibodies on pharmacokinetics, pharmacodynamics, safety, and/or effectiveness.Active Psoriatic ArthritisBy Week 28, approximately 12.1% (79/652) of adult subjects treated with SKYRIZI at the recommended dose developed antibodies to risankizumab-rzaa. None of the subjects who developed antibodies to risankizumab-rzaa had antibodies that were classified as neutralizing. Antibodies to risankizumab-rzaa were not associated with changes in clinical response for psoriatic arthritis. higher proportion of subjects with anti-drug antibodies experienced hypersensitivity reactions (6.3% (5/79)) and injection site reactions (2.5% (2/79)) compared to subjects without anti-drug antibodies (3.8% (22/574) with hypersensitivity reactions and 0.7% (4/574) with injection site reactions). None of these hypersensitivity and injection site reactions led to discontinuation of risankizumab-rzaa.Moderately to Severely Active Crohns DiseaseBy Week 64, antibodies to risankizumab-rzaa developed in approximately 3.4% (2/58) of subjects treated with SKYRIZI induction followed by 360 mg maintenance regimen. No subjects (0/57) treated with SKYRIZI induction followed by 180 mg maintenance regimen developed antibodies to risankizumab-rzaa. None of the subjects who developed antibodies to risankizumab-rzaa had antibodies that were classified as neutralizing.Moderately to Severely Active Ulcerative ColitisBy Week 64, antibodies to risankizumab-rzaa developed in approximately 8.9% (8/90) or 4.4% (4/91) of subjects treated with SKYRIZI induction followed by the 180 mg or 360 mg maintenance regimen, respectively. Of the subjects who developed antibodies to risankizumab-rzaa, 75% (6.7% of all subjects treated with SKYRIZI induction followed by the 180 mg maintenance regimen) or 50% (2.2% of all subjects treated with SKYRIZI induction followed by the 360 mg maintenance regimen), respectively, had antibodies that were classified as neutralizing.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical trials of drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Plaque PsoriasisA total of 2234 subjects were treated with SKYRIZI in clinical development trials in plaque psoriasis. Of these, 1208 subjects with psoriasis were exposed to SKYRIZI for at least one year. Data from placebo- and active-controlled trials were pooled to evaluate the safety of SKYRIZI for up to 16 weeks. In total, 1306 subjects were evaluated in the SKYRIZI 150 mg group. Table summarizes the adverse reactions that occurred at rate of at least 1% and at higher rate in the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials. Table 4. Adverse Reactions Occurring in >= 1% of Adults with Plaque Psoriasis on SKYRIZI through Week 16Adverse Drug ReactionsSKYRIZIN 1306n (%)PlaceboN 300n (%)Upper respiratory infectionsa 170 (13)29 (9.7)Headacheb 46 (3.5)6 (2) Fatiguec 33 (2.5)3 (1)Injection site reactionsd 19 (1.5)3 (1)Tinea infectionse 15 (1.1)1 (0.3)a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis Includes: headache, tension headache, sinus headache, cervicogenic headache Includes: fatigue, asthenia Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation, irritation, pain, pruritus, reaction, swelling, warmth Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection, onychomycosis Adverse reactions that occurred in 1% but 0.1% of subjects in the SKYRIZI group and at higher rate than in the placebo group through Week 16 were folliculitis and urticaria. Specific Adverse ReactionsInfections: In the first 16 weeks, infections occurred in 22.1% of the SKYRIZI group (90.8 events per 100 patient-years) compared with 14.7% of the placebo group (56.5 events per 100 patient-years) and did not lead to discontinuation of SKYRIZI. The rates of serious infections for the SKYRIZI group and the placebo group were <=0.4%. Serious infections in the SKYRIZI group included cellulitis, osteomyelitis, sepsis, and herpes zoster. In Trials PsO-1 and PsO-2, through Week 52, the rate of infections (73.9 events per 100 patient-years) was similar to the rate observed during the first 16 weeks of treatment. Safety Through Week 52Through Week 52, no new adverse reactions were identified, and the rates of the adverse reactions were similar to those observed during the first 16 weeks of treatment. During this period, serious infections that led to trial discontinuation included pneumonia. Plaque Psoriasis of the Scalp or Genital AreaThe overall safety profile observed in clinical trials of subjects with moderate-to-severe plaque psoriasis of the scalp or genital area treated with SKYRIZI is generally consistent with the safety profile observed in previous clinical trials of subjects with moderate-to-severe plaque psoriasis [see Clinical Studies 14.1 )].Adverse Reactions in Pediatric Subjects Years of Age and Older with Plaque PsoriasisThe safety of SKYRIZI was evaluated in four-part trial that included 137 pediatric subjects years of age and older with moderate-to-severe plaque psoriasis [see Clinical Studies 14.1 )]. Overall, the safety profile observed in pediatric subjects years of age and older treated with SKYRIZI for up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.Adverse Reactions in Adult Subjects with Psoriatic ArthritisThe overall safety profile observed in adult subjects with psoriatic arthritis treated with SKYRIZI is generally consistent with the safety profile in adult subjects with plaque psoriasis. Additionally, in the Phase placebo-controlled trials the incidence of hepatic events was higher in the SKYRIZI group (5.4%, 16.7 events per 100 patient-years) compared to the placebo group (3.9%, 12.6 events per 100 patient-years). Of these, the most common events that were reported more frequently in both the placebo group and the SKYRIZI group were ALT increased (placebo: n=12 (1.7%); SKYRIZI: n=16 (2.3%)), AST increased (placebo: n=9 (1.3%); SKYRIZI: n=13 (1.8%)), and GGT increased (placebo: n=5 (0.7%); SKYRIZI: n=8 (1.1%)). There were no serious hepatic events reported. The incidence of hypersensitivity reactions was higher in the SKYRIZI group (n=16, 2.3%) compared to the placebo group (n=9, 1.3%). In the Phase placebo-controlled trials, hypersensitivity reactions reported at higher rate in the SKYRIZI group included rash (placebo: n=4 (0.6%); SKYRIZI: n=5 (0.7%)), allergic rhinitis (placebo: n=1 (0.1%); SKYRIZI: n=2 (0.3%)), and facial swelling (placebo: n=0 (0.0%); SKYRIZI n=1 (0.1%)). One case of anaphylaxis was reported in subject who received SKYRIZI in the Phase clinical trial.Adverse Reactions in Adult Subjects with Crohns Disease SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohns disease in two randomized, double-blind, placebo-controlled induction trials (CD-1, CD-2) and randomized, double-blind, placebo-controlled, dose-finding trial (CD-4; NCT02031276). Long-term safety up to 52 weeks was evaluated in subjects who responded to induction therapy in randomized, double-blind, placebo-controlled maintenance trial (CD-3) [see Clinical Studies 14.3 )]. In the two induction trials (CD-1, CD-2) and the dose finding trial (CD-4), 620 subjects received the SKYRIZI intravenous induction regimen at Weeks 0, and 8. In the maintenance trial (CD-3), 297 subjects who achieved clinical response, defined as reduction in CDAI of at least 100 points from baseline after 12 weeks of induction treatment with intravenous SKYRIZI in trials CD-1 and CD-2, received maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every weeks thereafter for up to an additional 52 weeks.Adverse reactions reported in 3% of subjects in induction trials and at higher rate than placebo are shown in Table 5.Table 5. Adverse Drug Reactions Reported in 3% of Subjects with Crohns Disease Treated with SKYRIZI in Placebo-Controlled 12-Week Induction Trials (CD-1, CD-2, and CD-4)Adverse Drug ReactionsSKYRIZI600 mg Intravenous InfusionaN 620n (%)PlaceboN 432n (%)Upper respiratory infectionsb 66 (10.6)40 (9.3)Headachec 41 (6.6)24 (5.6)Arthralgia31 (5)19 (4.4)a SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8. Includes: influenza like illness, nasopharyngitis, influenza, pharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, COVID-19, nasal congestion, respiratory tract infection viral, viral pharyngitis, tonsillitis, upper respiratory tract inflammation Includes: headache, tension headacheAdverse reactions reported in >3% of subjects in the maintenance trial and at higher rate than placebo are shown in Table 6.Table 6. Adverse Reactions Reported in >3% of Subjects with Crohns Disease Treated with SKYRIZIa in Placebo-Controlled 52-Week Maintenance Trial (CD-3) Adverse Drug ReactionsSKYRIZI180 mg Subcutaneous InjectionN 155n (%)SKYRIZI360 mg Subcutaneous InjectionN 142n (%)PlaceboN 143n (%)Arthralgia13 (8.4)13 (9.2)12 (8.4)Abdominal painb (5.8)12 (8.5)6 (4.2)Injection site reactionsc,d (4.5)8 (5.6)4 (2.8) Anemia7 (4.5)7 (4.9)6 (4.2)Pyrexia4 (2.6)7 (4.9)4 (2.8)Back pain (1.9)6 (4.2)3 (2.1)Arthropathy1 (0.6)5 (3.5)2 (1.4)Urinary tract infection1 (0.6)5 (3.5)4 (2.8)a SKYRIZI 180 mg or 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks Includes: abdominal pain, abdominal pain upper, abdominal pain lower Includes: injection site rash, injection site erythema, injection site swelling, injection site urticaria, injection site warmth, injection site pain, injection site hypersensitivity, injection site reaction Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject for the rate calculations. Specific Adverse ReactionsInfections: In the maintenance trial (CD-3) through Week 52, the rate of infections was 32.3% (50.2 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 36.6% (60.8 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 36.4% (60.3 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. The rate of serious infections was 2.6% (2.7 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 5.6% (7.4 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 2.1% (2.4 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. Lipid Elevations: Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol [LDL-C]) were first assessed at weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from baseline and increases relative to placebo were observed at Week and remained stable to Week 12. Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to mean absolute value of 175.1 mg/dL at Week 12. Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to mean absolute value of 92.6 mg/dL at Week 12. Mean LDL-C increased by 3.1 mg/dL from baseline to mean absolute value of 99 mg/dL at Week 52 with SKYRIZI 180 mg maintenance treatment and by 2.3 mg/dL from baseline to mean absolute value of 102.2 mg/dL at Week 52 with SKYRIZI 360 mg maintenance treatment (CD-3). Adverse Reactions in Adult Subjects with Ulcerative Colitis SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active ulcerative colitis in randomized, double-blind, placebo-controlled induction trial (UC-1) and randomized, double-blind, placebo-controlled, dose-finding trial (UC-3). Long-term safety up to 52 weeks was evaluated in subjects who responded to induction therapy in randomized, double-blind, placebo-controlled maintenance trial (UC-2) [see Clinical Studies 14.4 )]. In the induction trials (UC-1 and UC-3), 712 subjects received the SKYRIZI 1,200 mg intravenous induction regimen at Weeks 0, and 8. In the maintenance trial (UC-2), 347 subjects who achieved clinical response, defined as decrease in mMS of >=2 points and >=30% from baseline and decrease in RBS >=1 from baseline or an absolute RBS <=1, received maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every weeks thereafter for up to an additional 52 weeks.The adverse reaction reported in >=3% subjects treated with SKYRIZI in the ulcerative colitis induction trials (UC-1 and UC-3) and at higher rate than placebo was arthralgia (3% SKYRIZI vs 1% placebo). Adverse reactions reported in >=3% of subjects treated with SKYRIZI in the maintenance trial (UC-2) and at higher rate than placebo are shown in Table 7.Table 7. Adverse Reactions Reported in >=3% of Subjects with Ulcerative Colitis Treated with SKYRIZIa in Placebo-Controlled 52-Week Maintenance Trial (UC-2) Adverse Drug ReactionsSKYRIZI180 mg Subcutaneous InjectionN 170n (%)SKYRIZI360 mg Subcutaneous InjectionN 177n (%)PlaceboN 173n (%)Arthralgia9 (5.3)17 (9.6)8 (4.6)Pyrexia8 (4.7)7 (4)6 (3.5)Injection site reactionsb,c (2.9) (2.8) (1.2)Rashd (4.1) (0.6) (1.7)a SKYRIZI 180 mg or 360 mg at Week 12 and every weeks thereafter for up to an additional 52 weeks Includes: application site pain, injection site erythema, injection site pain, injection site pruritus, injection site reaction Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject for the rate calculations. Includes: rash and rash macularSpecific Adverse ReactionsThe rates of infections, serious infections, and lipid elevations in subjects with UC who received SKYRIZI compared to subjects who received placebo in the induction trials (UC-1 and UC-3) and maintenance trial (UC-2) were similar to the rates in subjects with CD who received SKYRIZI compared to subjects who received placebo in the induction trials (CD-1, CD-2, and CD-4) and maintenance trial (CD-3). Infections: In the maintenance trial (CD-3) through Week 52, the rate of infections was 32.3% (50.2 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 36.6% (60.8 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 36.4% (60.3 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. The rate of serious infections was 2.6% (2.7 events per 100 patient-years) in subjects who received SKYRIZI 180 mg and 5.6% (7.4 events per 100 patient-years) in subjects who received SKYRIZI 360 mg compared to 2.1% (2.4 events per 100 patient-years) in subjects who received placebo after SKYRIZI induction. Lipid Elevations: Elevations in lipid parameters (total cholesterol and low-density lipoprotein cholesterol [LDL-C]) were first assessed at weeks following initiation of SKYRIZI in the induction trials (CD-1, CD-2). Increases from baseline and increases relative to placebo were observed at Week and remained stable to Week 12. Following SKYRIZI induction, mean total cholesterol increased by 9.4 mg/dL from baseline to mean absolute value of 175.1 mg/dL at Week 12. Similarly, mean LDL-C increased by 6.6 mg/dL from baseline to mean absolute value of 92.6 mg/dL at Week 12. Mean LDL-C increased by 3.1 mg/dL from baseline to mean absolute value of 99 mg/dL at Week 52 with SKYRIZI 180 mg maintenance treatment and by 2.3 mg/dL from baseline to mean absolute value of 102.2 mg/dL at Week 52 with SKYRIZI 360 mg maintenance treatment (CD-3).

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. SKYRIZI is contraindicated in patients with history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients [see Warnings and Precautions 5.1 )].. SKYRIZI is contraindicated in patients with history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients (4) SKYRIZI is contraindicated in patients with history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Risankizumab-rzaa, an interleukin-23 (IL-23) antagonist, is humanized immunoglobulin G1 (IgG1) monoclonal antibody. Risankizumab-rzaa is produced by recombinant DNA technology in Chinese hamster ovary cells and has an approximate molecular weight of 149 kDa. SKYRIZI (risankizumab-rzaa) injection 55 mg/0.37 mL prefilled syringe for subcutaneous useEach SKYRIZI prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each syringe delivers 55 mg of risankizumab-rzaa and the inactive ingredients glacial acetic acid (0.02 mg), polysorbate 20 (0.07 mg), sodium acetate (0.28 mg), trehalose (23.4 mg), and Water for Injection, USP. The pH is 5.7. SKYRIZI (risankizumab-rzaa) injection 90 mg/mL prefilled syringe for subcutaneous useEach SKYRIZI prefilled syringe contains sterile, preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution. Each syringe delivers 90 mg of risankizumab-rzaa, and inactive ingredients polysorbate 20 (0.2 mg), sodium succinate (0.63 mg), sorbitol (41 mg), succinic acid (0.059 mg), and Water for Injection, USP. The pH is 6.2.SKYRIZI (risankizumab-rzaa) injection 150 mg/mL prefilled syringe or prefilled pen for subcutaneous use Each SKYRIZI prefilled pen or prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each syringe and pen delivers 150 mg of risankizumab-rzaa and the inactive ingredients glacial acetic acid (0.054 mg), polysorbate 20 (0.2 mg), sodium acetate (0.75 mg), trehalose (63.33 mg), and Water for Injection, USP. The pH is 5.7.SKYRIZI (risankizumab-rzaa) injection 180 mg/1.2 mL prefilled syringe for subcutaneous useEach SKYRIZI prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each syringe delivers 180 mg of risankizumab-rzaa, and inactive ingredients glacial acetic acid (0.065 mg), polysorbate 20 (0.24 mg), sodium acetate (0.898 mg), trehalose (76 mg), and Water for Injection, USP. The pH is 5.7.SKYRIZI (risankizumab-rzaa) injection 180 mg/1.2mL (150 mg/mL) prefilled cartridge for use with supplied on-body-injector for subcutaneous useEach SKYRIZI prefilled cartridge contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each cartridge delivers 180 mg of risankizumab-rzaa, and the inactive ingredients glacial acetic acid (0.065 mg), polysorbate 20 (0.24 mg), sodium acetate (0.9 mg), trehalose (76 mg), and Water for Injection, USP. The pH is 5.7.SKYRIZI (risankizumab-rzaa) injection 360 mg/2.4 mL (150 mg/mL) prefilled cartridge for use with the supplied on-body injector for subcutaneous use Each SKYRIZI prefilled cartridge contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each cartridge delivers 360 mg of risankizumab-rzaa, and the inactive ingredients glacial acetic acid (0.13 mg), polysorbate 20 (0.48 mg), sodium acetate (1.8 mg), trehalose (152 mg), and Water for Injection, USP. The pH is 5.7.SKYRIZI 600 mg/10 mL (60 mg/mL) in vial for intravenous infusionSKYRIZI (risankizumab-rzaa) injection 600 mg/10 mL (60 mg/mL) is sterile, preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution in 10 mL single-dose vial.Each 10 mL single-dose vial contains 600 mg of risankizumab-rzaa, and the inactive ingredients glacial acetic acid (0.54 mg), polysorbate 20 (2 mg), sodium acetate (7.5 mg), trehalose (633.3 mg), and Water for Injection, USP. The pH is 5.7.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. For the treatment of moderately to severely active Crohns disease and ulcerative colitis: Obtain liver enzymes and bilirubin levels prior to initiating treatment with SKYRIZI. (2.1, 5.4) Complete all age-appropriate vaccinations as recommended by current immunization guidelines (2.1, 5.5)Recommended DosageModerate-to-Severe Plaque Psoriasis:Adults:150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3)Pediatric Patients Years of Age and Older:Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3)Active Psoriatic Arthritis:Adults:150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) Pediatric Patients Years of Age and Older:Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4)SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs). (2.4)Moderately to Severely Active Crohns Disease:The recommended induction dosage is 600 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage to maintain therapeutic response. (2.6) Moderately to Severely Active Ulcerative Colitis:The recommended induction dosage is 1,200 mg administered by intravenous infusion over at least two hours at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage to maintain therapeutic response. (2.7). For the treatment of moderately to severely active Crohns disease and ulcerative colitis: Obtain liver enzymes and bilirubin levels prior to initiating treatment with SKYRIZI. (2.1, 5.4) Complete all age-appropriate vaccinations as recommended by current immunization guidelines (2.1, 5.5). Adults:150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3). 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3). Pediatric Patients Years of Age and Older:Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3). Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.3). Adults:150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) Pediatric Patients Years of Age and Older:Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4). Patients weighing less than 40 kg: 55 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4) Patients weighing 40 kg or greater: 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. (2.4). SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs). (2.4). The recommended induction dosage is 600 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage to maintain therapeutic response. (2.6) The recommended induction dosage is 1,200 mg administered by intravenous infusion over at least two hours at Week 0, Week 4, and Week 8. The recommended maintenance dosage is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage to maintain therapeutic response. (2.7). 2.1 Procedures Prior to Treatment Initiation. For the treatment of moderately to severely active Crohns disease and ulcerative colitis, obtain liver enzymes and bilirubin levels prior to initiating treatment with SKYRIZI [see Warnings and Precautions 5.4 )]. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI [see Warnings and Precautions 5.3 )]. Complete all age-appropriate vaccinations as recommended by current immunization guidelines [see Warnings and Precautions 5.5 )].. For the treatment of moderately to severely active Crohns disease and ulcerative colitis, obtain liver enzymes and bilirubin levels prior to initiating treatment with SKYRIZI [see Warnings and Precautions 5.4 )]. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI [see Warnings and Precautions 5.3 )]. Complete all age-appropriate vaccinations as recommended by current immunization guidelines [see Warnings and Precautions 5.5 )].. 2.2 General Considerations for Administration. Visually inspect SKYRIZI for particulate matter and discoloration prior to administration. The solution may contain few translucent to white particles. SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe, 180 mg/1.2 mL prefilled syringe or prefilled cartridge, and 360 mg/2.4 mL prefilled cartridge: colorless to yellow, and clear to slightly opalescent solution. SKYRIZI 90 mg/mL prefilled syringe and 600 mg/10 mL vial: colorless to slightly yellow, and clear to slightly opalescent solution. Do not use if the solution contains large particles or is cloudy or discolored.o Discard after use. Do not reuse.. 2.3 Recommended Dosage for Moderate-to-Severe Plaque Psoriasis. AdultsThe recommended dosage for adults is 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. Pediatric Patients Years of Age and OlderThe recommended dosage for pediatric patients years of age and older is based on body weight (see Table 1) and administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. Table 1. Recommended Dose of SKYRIZI for Pediatric Patients Years of Age and Older with Moderate-to-Severe Plaque PsoriasisBody WeightRecommended Doseless than 40 kg55 mg40 kg or greater150 mg. 2.4 Recommended Dosage for Active Psoriatic Arthritis AdultsThe recommended dosage for adult patients is 150 mg administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.SKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).Pediatric Patients Years of Age and OlderThe recommended dosage for pediatric patients years of age and older is based on body weight (see Table 2) and administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter. Table 2. Recommended Dose of SKYRIZI for Pediatric Patients Years of Age and Older with Active Psoriatic ArthritisBody WeightRecommended Doseless than 40 kg55 mg40 kg or greater150 mgSKYRIZI may be administered alone or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).. 2.5 Preparation and Administration Instructions (Moderate-to-Severe Plaque Psoriasis and Active Psoriatic Arthritis). Administer SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe subcutaneously.o Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI. After proper training: Adults Adults may self-inject SKYRIZI. Pediatric Patients Years of Age and Older For pediatric patients 10 years of age and older, it is recommended that SKYRIZI be administered by or under the supervision of an adult. For pediatric patients to less than 10 years of age, SKYRIZI should be administered by an adult.Before injecting, remove the carton with SKYRIZI from the refrigerator and without removing the prefilled pen or prefilled syringe from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (30 to 90 minutes for the prefilled pen and 15 to 30 minutes for the prefilled syringe). Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of SKYRIZI in the upper, outer arm may only be performed by healthcare professional or caregiver. If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.The SKYRIZI Instructions for Use contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use ]. Instruct the patient to read the Instructions for Use before administration.. Before injecting, remove the carton with SKYRIZI from the refrigerator and without removing the prefilled pen or prefilled syringe from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (30 to 90 minutes for the prefilled pen and 15 to 30 minutes for the prefilled syringe). Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of SKYRIZI in the upper, outer arm may only be performed by healthcare professional or caregiver. If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.. 2.6 Recommended Dosage for Moderately to Severely Active Crohns Disease. Adult Patients: InductionThe recommended induction dosage of SKYRIZI is 600 mg administered by intravenous infusion over period of at least one hour at Week 0, Week 4, and Week 8.Adult Patients: MaintenanceThe recommended maintenance dosage of SKYRIZI is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage needed to maintain therapeutic response.. 2.7 Recommended Dosage for Moderately to Severely Active Ulcerative Colitis. Adult Patients: InductionThe recommended induction dosage of SKYRIZI is 1,200 mg administered by intravenous infusion over period of at least two hours at Week 0, Week 4, and Week 8. Adult Patients: MaintenanceThe recommended maintenance dosage of SKYRIZI is 180 mg or 360 mg administered by subcutaneous injection at Week 12, and every weeks thereafter. Use the lowest effective dosage needed to maintain therapeutic response.. 2.8 Preparation and Administration Instructions (Moderately to Severely Active Crohns Disease and Ulcerative Colitis). Intravenous Induction Dosing Regimen:1. SKYRIZI vial for intravenous administration is intended for administration by healthcare provider using aseptic technique. 2. Prior to intravenous administration, determine the dose and number of SKYRIZI vials needed based on the patients indication (see table below). Withdraw 10 mL of SKYRIZI solution from vial (600 mg/10 mL) and inject into an intravenous infusion bag or glass bottle containing 5% Dextrose Injection or 0.9% Sodium Chloride Injection (see Table below) for final concentration of approximately 1.2 mg/mL to mg/mL. Discard any remaining solution in the vial.Table 3. Total Volume of Diluent Required for Intravenous Induction DoseIndicationIntravenous Induction DoseNumber of SKYRIZI 600 mg/10 mL VialsTotal Volume of 5% Dextrose or 0.9% Sodium Chloride InjectionCrohns disease600 mg1100 mL, or 250 mL, or 500 mLUlcerative colitis1,200 mg2250 mL, or 500 mL 3. Infuse the diluted solution intravenously over period of at least one hour for the SKYRIZI 600 mg dose; at least two hours for the SKYRIZI 1,200 mg dose. If stored refrigerated, allow the diluted SKYRIZI solution in the infusion bag or glass bottle to warm to room temperature prior to the start of the intravenous infusion.4. Do not administer SKYRIZI diluted solution concomitantly in the same intravenous line with other medicinal products.Handling and Storage of the Vial and the Diluted Solution: Do not shake the vial or diluted solution in the infusion bag or glass bottle. Use the prepared infusion immediately. If not used immediately, store the diluted SKYRIZI solution refrigerated and protected from light for up to 20 hours between 36F to 46F (2C to 8C). Immediately after preparation or removal from refrigeration, the diluted SKYRIZI solution can be stored at room temperature at up to 77F (25C) (protected from sunlight) for up to hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within hours after dilution in the infusion bag. Exposure to indoor light is acceptable during room temperature storage and administration. Do not freeze.Subcutaneous Maintenance Dosing Regimen: Using the single-dose 180 mg or 360 mg prefilled cartridge with On-Body Injector: SKYRIZI is intended for use under the guidance and supervision of healthcare professional. Patients may self-inject SKYRIZI using the on-body injector with prefilled cartridge after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI. Before using the on-body injector with prefilled cartridge, remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (45 to 90 minutes) without removing the prefilled cartridge or on-body injector from the carton. Use the on-body injector to administer SKYRIZI 180 mg/1.2 mL or SKYRIZI 360 mg/2.4 mL prefilled cartridge subcutaneously on thigh or abdomen. Start the injection within minutes after inserting the prefilled cartridge into the On-Body Injector. Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions. If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.The SKYRIZI Instructions for Use contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use ]. Instruct the patient to read the Instructions for Use before administration.Using the 90 mg/mL or 180 mg/1.2 mL prefilled syringe:o Administer each SKYRIZI 90 mg/mL or 180 mg/1.2 mL prefilled syringe subcutaneously.o Patients may self-inject SKYRIZI after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI.o Before injecting, remove the carton from the refrigerator and without removing the prefilled syringes from the carton, allow SKYRIZI to reach room temperature out of direct sunlight (15 to 30 minutes).o Use the 90 mg/mL or 180 mg/1.2 mL prefilled syringe(s) to administer SKYRIZI 180 mg or SKYRIZI 360 mg subcutaneously as follows: 180 mg maintenance dose: SKYRIZI 90 mg/mL prefilled syringes: Two 90 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen). SKYRIZI 180 mg/1.2 mL prefilled syringe: One 180 mg prefilled syringe is required. 360 mg maintenance dose: SKYRIZI 90 mg/mL prefilled syringes: Four 90 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen). SKYRIZI 180 mg/1.2 mL prefilled syringes: Two 180 mg prefilled syringes are required. Inject one prefilled syringe after the other in different anatomic locations (such as thighs or abdomen).o Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions. Administration of SKYRIZI in the upper, outer arm may only be performed by healthcare professional or caregiver.o If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.The SKYRIZI Instructions for Use contains more detailed instructions on the preparation and administration of SKYRIZI [see Instructions for Use ]. Instruct the patient to read the Instructions for Use before administration.. Do not shake the vial or diluted solution in the infusion bag or glass bottle. Use the prepared infusion immediately. If not used immediately, store the diluted SKYRIZI solution refrigerated and protected from light for up to 20 hours between 36F to 46F (2C to 8C). Immediately after preparation or removal from refrigeration, the diluted SKYRIZI solution can be stored at room temperature at up to 77F (25C) (protected from sunlight) for up to hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within hours after dilution in the infusion bag. Exposure to indoor light is acceptable during room temperature storage and administration. Do not freeze.. SKYRIZI is intended for use under the guidance and supervision of healthcare professional. Patients may self-inject SKYRIZI using the on-body injector with prefilled cartridge after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of SKYRIZI. Before using the on-body injector with prefilled cartridge, remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (45 to 90 minutes) without removing the prefilled cartridge or on-body injector from the carton. Use the on-body injector to administer SKYRIZI 180 mg/1.2 mL or SKYRIZI 360 mg/2.4 mL prefilled cartridge subcutaneously on thigh or abdomen. Start the injection within minutes after inserting the prefilled cartridge into the On-Body Injector. Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions. If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Subcutaneous InjectionSKYRIZI PenInjection: 150 mg/mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled pen.SKYRIZI Prefilled SyringeInjection: 55 mg/0.37 mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 90 mg/mL as colorless to slightly yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 150 mg/mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.SKYRIZI Prefilled Cartridge with Supplied On-Body InjectorInjection: 180 mg/1.2 mL (150 mg/mL) as colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector. Injection: 360 mg/2.4 mL (150 mg/mL) as colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector.Intravenous InfusionSKYRIZI VialInjection: 600 mg/10 mL (60 mg/mL) as colorless to slightly yellow, and clear to slightly opalescent solution in each single-dose vial.. Injection: 150 mg/mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled pen.. Injection: 55 mg/0.37 mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 90 mg/mL as colorless to slightly yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 150 mg/mL as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) as colorless to yellow and clear to slightly opalescent solution in each single-dose prefilled syringe.. Injection: 180 mg/1.2 mL (150 mg/mL) as colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector. Injection: 360 mg/2.4 mL (150 mg/mL) as colorless to yellow, and clear to slightly opalescent solution in each single-dose prefilled cartridge for use with the on-body injector.. Injection: 600 mg/10 mL (60 mg/mL) as colorless to slightly yellow, and clear to slightly opalescent solution in each single-dose vial.. Subcutaneous injection (3)Injection: 150 mg/mL in each single-dose prefilled pen. Injection: 55 mg/0.37 mL in each single-dose prefilled syringe. Injection: 90 mg/mL in each single-dose prefilled syringe. Injection: 150 mg/mL in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) in each single-dose prefilled cartridge. Injection: 360 mg/2.4 mL (150 mg/mL) in each single-dose prefilled cartridge.Intravenous infusion (3)Injection: 600 mg/10 mL (60 mg/mL) in each single-dose vial.. Injection: 150 mg/mL in each single-dose prefilled pen. Injection: 55 mg/0.37 mL in each single-dose prefilled syringe. Injection: 90 mg/mL in each single-dose prefilled syringe. Injection: 150 mg/mL in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) in each single-dose prefilled syringe. Injection: 180 mg/1.2 mL (150 mg/mL) in each single-dose prefilled cartridge. Injection: 360 mg/2.4 mL (150 mg/mL) in each single-dose prefilled cartridge.. Injection: 600 mg/10 mL (60 mg/mL) in each single-dose vial.

GERIATRIC USE SECTION.

8.5 Geriatric Use. Of the 6,862 subjects exposed to SKYRIZI, total of 664 were 65 years and older (243 subjects with plaque psoriasis, 246 subjects with psoriatic arthritis, 72 subjects with Crohns disease and 103 subjects with ulcerative colitis), and 71 subjects were 75 years and older. Clinical studies of SKYRIZI, within each indication, did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed based on age [see Clinical Pharmacology 12.3 )].

HEPATIC IMPAIRMENT SUBSECTION.

5.4 Hepatotoxicity A serious adverse reaction of drug-induced liver injury in conjunction with rash that required hospitalization was reported in patient with Crohns disease (ALT 54x ULN, AST 30x ULN, and total bilirubin 2.2x ULN) following two 600 mg intravenous doses of SKYRIZI. The liver test abnormalities resolved following administration of steroids. SKYRIZI was subsequently discontinued.For the treatment of Crohns disease and ulcerative colitis, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedSKYRIZI (risankizumab-rzaa) injection is supplied in the following strengths and packaging units:StrengthPackaging UnitNDCSubcutaneous Injection150 mg/mL single-dose penCarton of 10074-2100-0155 mg/0.37 mL single-dose prefilled syringeCarton of 10074-4059-0190 mg/mL single-dose prefilled syringeCarton of 20074-7040-02Carton of 40074-7042-04180 mg/1.2 mL (150 mg/mL) single-dose prefilled syringeCarton of 10074-8300-01Carton of 20074-8350-01150 mg/mL single-dose prefilled syringeCarton of 10074-1050-01180 mg/1.2 mL (150 mg/mL) single-dose prefilled cartridge with on-body injectorKit0074-1065-01360 mg/2.4 mL (150 mg/mL) single-dose prefilled cartridge with on-body injectorKit 0074-1070-01Intravenous Infusion600 mg/10 mL (60 mg/mL) single-dose vialCarton of 0074-5015-01Subcutaneous InjectionSKYRIZI 55 mg/0.37 mL prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe consists of 1 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 150 mg/mL prefilled syringe or prefilled pen contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe or prefilled pen consists of 1 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 90 mg/mL prefilled syringe contains sterile, preservative-free, colorless to slightly yellow and clear to slightly opalescent solution. Each prefilled syringe consists of 1 mL glass syringe with fixed 29-gauge 1/2 inch needle with needle guard. SKYRIZI 180 mg/1.2 mL (150 mg/mL) prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe consists of 2.25 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 180 mg/1.2 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with septum and cap contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. SKYRIZI 360 mg/2.4 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with septum and cap contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Intravenous InfusionSKYRIZI 600 mg/10 mL (60 mg/mL) vial contains sterile and preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution. Each glass vial is closed with stopper and blue flip cap.Storage and HandlingStore in refrigerator at 36F to 46 (2C to 8C). Do not freeze. Do not shake. Keep in the original cartons to protect from light. Not made with natural rubber latex.. SKYRIZI 55 mg/0.37 mL prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe consists of 1 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 150 mg/mL prefilled syringe or prefilled pen contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe or prefilled pen consists of 1 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 90 mg/mL prefilled syringe contains sterile, preservative-free, colorless to slightly yellow and clear to slightly opalescent solution. Each prefilled syringe consists of 1 mL glass syringe with fixed 29-gauge 1/2 inch needle with needle guard. SKYRIZI 180 mg/1.2 mL (150 mg/mL) prefilled syringe contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe consists of 2.25 mL glass syringe with fixed 27-gauge 1/2 inch needle with needle guard. SKYRIZI 180 mg/1.2 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with septum and cap contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. SKYRIZI 360 mg/2.4 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with septum and cap contains sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Store in refrigerator at 36F to 46 (2C to 8C). Do not freeze. Do not shake. Keep in the original cartons to protect from light. Not made with natural rubber latex.

IMMUNOGENICITY.

12.6 Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the trials described below with the incidence of ADA in other trials, including those of SKYRIZI or other risankizumab products. Moderate-to-Severe Plaque PsoriasisBy Week 52, approximately 24% (263/1079) of adults treated with SKYRIZI at the recommended dosage developed antibodies to risankizumab-rzaa. Of the subjects who developed antibodies to risankizumab-rzaa, approximately 57% (14% of all subjects treated with SKYRIZI) had antibodies that were classified as neutralizing. Higher antibody titers in approximately 1% of subjects treated with SKYRIZI were associated with lower risankizumab-rzaa concentrations and reduced clinical response. In pediatric subjects years of age and older, approximately 15% (13/88) of subjects treated with SKYRIZI at the recommended dose developed antibodies to risankizumab-rzaa by Week 52. Of the 13 subjects who developed antibodies to risankizumab-rzaa, approximately 15% (2.3% of all subjects treated with SKYRIZI) had antibodies that were classified as neutralizing. Due to the small number of subjects who developed antibodies to risankizumab-rzaa, it is difficult to determine the impact of the antibodies on pharmacokinetics, pharmacodynamics, safety, and/or effectiveness.Active Psoriatic ArthritisBy Week 28, approximately 12.1% (79/652) of adult subjects treated with SKYRIZI at the recommended dose developed antibodies to risankizumab-rzaa. None of the subjects who developed antibodies to risankizumab-rzaa had antibodies that were classified as neutralizing. Antibodies to risankizumab-rzaa were not associated with changes in clinical response for psoriatic arthritis. higher proportion of subjects with anti-drug antibodies experienced hypersensitivity reactions (6.3% (5/79)) and injection site reactions (2.5% (2/79)) compared to subjects without anti-drug antibodies (3.8% (22/574) with hypersensitivity reactions and 0.7% (4/574) with injection site reactions). None of these hypersensitivity and injection site reactions led to discontinuation of risankizumab-rzaa.Moderately to Severely Active Crohns DiseaseBy Week 64, antibodies to risankizumab-rzaa developed in approximately 3.4% (2/58) of subjects treated with SKYRIZI induction followed by 360 mg maintenance regimen. No subjects (0/57) treated with SKYRIZI induction followed by 180 mg maintenance regimen developed antibodies to risankizumab-rzaa. None of the subjects who developed antibodies to risankizumab-rzaa had antibodies that were classified as neutralizing.Moderately to Severely Active Ulcerative ColitisBy Week 64, antibodies to risankizumab-rzaa developed in approximately 8.9% (8/90) or 4.4% (4/91) of subjects treated with SKYRIZI induction followed by the 180 mg or 360 mg maintenance regimen, respectively. Of the subjects who developed antibodies to risankizumab-rzaa, 75% (6.7% of all subjects treated with SKYRIZI induction followed by the 180 mg maintenance regimen) or 50% (2.2% of all subjects treated with SKYRIZI induction followed by the 360 mg maintenance regimen), respectively, had antibodies that were classified as neutralizing.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. SKYRIZI is an interleukin-23 antagonist indicated for the treatment of:moderate-to-severe plaque psoriasis in adults and pediatric patients years of age and older who are candidates for systemic therapy or phototherapy. (1.1) active psoriatic arthritis in adults and pediatric patients years of age and older. (1.2) moderately to severely active Crohns disease in adults. (1.3) moderately to severely active ulcerative colitis in adults. (1.4). moderate-to-severe plaque psoriasis in adults and pediatric patients years of age and older who are candidates for systemic therapy or phototherapy. (1.1) active psoriatic arthritis in adults and pediatric patients years of age and older. (1.2) moderately to severely active Crohns disease in adults. (1.3) moderately to severely active ulcerative colitis in adults. (1.4). 1.1 Plaque Psoriasis. SKYRIZI(R) is indicated for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients years of age and older who are candidates for systemic therapy or phototherapy. 1.2 Psoriatic Arthritis. SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults and pediatric patients years of age and older.. 1.3 Crohns Disease. SKYRIZI is indicated for the treatment of moderately to severely active Crohns disease in adults.. 1.4 Ulcerative Colitis. SKYRIZI is indicated for the treatment of moderately to severely active ulcerative colitis in adults.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise patients and/or caregivers to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Hypersensitivity ReactionsAdvise patients to discontinue SKYRIZI and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions 5.1 )]. InfectionsInform patients that SKYRIZI may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection [see Warnings and Precautions 5.2 )]. Hepatotoxicity Inform patients that SKYRIZI may cause liver injury, especially during the initial 12 weeks of treatment. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction (e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine) [see Warnings and Precautions 5.4 )] ImmunizationsAdvise patients that vaccination with live vaccines is not recommended during SKYRIZI treatment and immediately prior to or after SKYRIZI treatment. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Instruct patients to inform the healthcare practitioner that they are taking SKYRIZI prior to potential vaccination [see Warnings and Precautions 5.5 ].Administration InstructionInstruct patients or caregivers to perform the first self-injected dose under the supervision and guidance of qualified healthcare professional for training in preparation and administration of SKYRIZI, including choosing anatomical sites for administration, and proper subcutaneous injection technique [see Dosage and Administration 2.5 )]. For pediatric patients, inform patients and caregivers that for pediatric patients 10 years of age and older, it is recommended that SKYRIZI be administered by or under supervision of an adult. For pediatric patients to less than 10 years of age, SKYRIZI should be administered by an adult [see Dosage and Administration 2.5 )].If using SKYRIZI 90 mg/mL, instruct patients or caregivers to administer two 90 mg single-dose syringes to achieve the full 180 mg maintenance dose or four 90 mg single-dose syringes to achieve the full 360 mg maintenance dose of SKYRIZI for Crohns disease or ulcerative colitis [see Instructions for Use ]. If using SKYRIZI 180 mg/1.2 mL, instruct patients or caregivers to administer one 180 mg single-dose syringe to achieve the full 180 mg maintenance dose or two 180 mg single-dose syringes to achieve the full 360 mg maintenance dose of SKYRIZI for Crohns disease or ulcerative colitis [see Instructions for Use ]. Instruct patients or caregivers in the technique of pen or syringe disposal [see Instructions for Use ]. PregnancyAdvise patients that there is pregnancy registry that monitors pregnancy outcomes in women exposed to SKYRIZI during pregnancy [see Use in Specific Populations 8.1 ].Manufactured by:AbbVie Inc.North Chicago, IL 60064, USA US License Number 1889SKYRIZI and its design are trademarks of AbbVie Biotechnology Ltd.(C) 2026 AbbVie. All rights reserved.20101630 6/2026.

INSTRUCTIONS FOR USE SECTION.

INSTRUCTIONS FOR USESKYRIZI(R) (sky-RIZZ-ee) Pen(risankizumab-rzaa)injection, for subcutaneous usesingle-dose prefilled pen150 mg/mLRead Before First UseRefer to the Medication Guide for product information.Read complete Instructions for Use before using SKYRIZI Pen (risankizumab-rzaa) injection.Before using SKYRIZI, you should receive training from your healthcare provider on how to inject SKYRIZI Pen.In children 10 years of age and older, it is recommended that SKYRIZI Pen be given by an adult or with an adult watching (supervision).In children years to less than 10 years of age, SKYRIZI should be given by an adult. SKYRIZI Pen Important Information You Need to Know Before Injecting SKYRIZI PenStore SKYRIZI Pen in the refrigerator between 36F to 46F (2C to 8C). Keep SKYRIZI Pen in the original carton to protect from light until you are ready to use. Before injecting, take the SKYRIZI Pen carton out of the refrigerator. Leave the carton at room temperature and out of direct sunlight for 30 to 90 minutes.The liquid in the inspection window should look clear to yellow and may contain tiny white or clear particles. Do not use SKYRIZI Pen if the liquid is discolored, cloudy or contains flakes or large particles. Do not use SKYRIZI Pen if the expiration date (EXP) has passed. Do not use SKYRIZI Pen if the liquid has been frozen, even if it has been thawed. Do not shake SKYRIZI Pen. Do not use if the SKYRIZI Pen has been dropped or damaged. Do not use SKYRIZI Pen if carton perforations are broken. Return product to pharmacy.Do not remove the dark gray cap until right before injection. SKYRIZI Pen is not made with natural rubber latex.Prepare SKYRIZI Pen injection Take the SKYRIZI Pen carton out of the refrigerator. Leave the carton at room temperature and out of direct sunlight for 30 to 90 minutes before injecting. Do not remove the SKYRIZI Pen from the carton while allowing SKYRIZI to reach room temperature. Do not warm SKYRIZI Pen in any other way. For example, do not warm it in microwave or in hot water. Do not use the SKYRIZI Pen if the liquid has been frozen, even if it has been thawed. Check expiration date (EXP). Do not use the SKYRIZI Pen if expiration date has passed. Gather and Place the following on clean, flat surface: single-dose SKYRIZI Pen (included) alcohol swab (not included) cotton ball or gauze pad (not included) Sharps disposal container (not included). See Used SKYRIZI Pen Disposal for information on how to throw away (dispose of) used SKYRIZI Pens. Wash and dry your hands. Choose an injection site: on the front of your left thigh or right thigh or your abdomen (belly) at least inches from your navel (belly button) ipe the injection site in circular motion with the alcohol swab and let it dry. Do not touch or blow on the injection site after it is cleaned. Allow the skin to dry before injecting. Do not inject through clothes. Do not inject into skin that is sore, bruised, red, hard, scarred, has stretch marks, or areas with psoriasis. Hold the SKYRIZI Pen with the dark gray cap pointing up. Pull the dark gray cap straight off.Throw the dark gray cap away. Check the liquid through the inspection window. It is normal to see or more bubbles in the liquid. The liquid should look clear to yellow and may contain tiny white or clear particles. Do not use if the liquid is discolored, cloudy or contains flakes or large particles. Give SKYRIZI Pen injection Hold the SKYRIZI Pen with your fingers on the gray hand grips.Turn the SKYRIZI Pen so that the white needle sleeve points toward the injection site and you can see the green activator button. Pinch the skin at your injection site to make raised area and hold it firmly. Place the white needle sleeve straight (90-degree angle) against the raised injection site. Hold the SKYRIZI Pen so that you can see the green activator button and inspection window. Push and keep pressing the SKYRIZI Pen down firmly against the raised injection site. The SKYRIZI Pen will activate only if the white needle sleeve is pressed down against the injection site before pressing the green activator button. Press the green activator button and hold the SKYRIZI Pen for 15 seconds. The first loud click means the start of the injection. Keep pressing the SKYRIZI Pen down firmly against the injection site until the injection is complete.This takes up to 15 seconds.The injection is complete when: the SKYRIZI Pen has made second click or the yellow indicator has filled the inspection window After SKYRIZI Pen injectionWhen the injection is complete, slowly pull the SKYRIZI Pen straight out from the skin. The white needle sleeve will cover the needle tip and make another click. After completing the injection, place cotton ball or gauze pad on the skin at the injection site. Do not rub the injection site. Slight bleeding at the injection site is normal. Throw away (dispose of) the used SKYRIZI Pen in sharps disposal container right away after use. Do not dispose of used SKYRIZI Pens in your household trash unless your community guidelines permit this. Do not recycle your sharps disposal container.The dark gray cap, alcohol swab, cotton ball or gauze pad, and packaging may be placed in your household trash.For more information see Used SKYRIZI Pen Disposal section located on the other side of the instructions. Important Information You Need to Know Before Injecting SKYRIZI PenBefore injecting, take the SKYRIZI Pen carton out of the refrigerator. Leave the carton at room temperature and out of direct sunlight for 30 to 90 minutes. The liquid in the inspection window should look clear to yellow and may contain tiny white or clear particles. Do not use SKYRIZI Pen if the liquid is discolored, cloudy or contains flakes or large particles. Do not use SKYRIZI Pen if the expiration date (EXP) has passed. Do not use if the SKYRIZI Pen has been dropped or damaged. Do not use SKYRIZI Pen if carton perforations are broken. Return product to pharmacy. Do not remove the dark gray cap until right before injection. SKYRIZI Pen is not made with natural rubber latex.Storage Information Store SKYRIZI Pen in the refrigerator between 36F to 46F (2C to 8C). Keep SKYRIZI Pen in the original carton to protect from light until you are ready to use. Do not use SKYRIZI Pen if the liquid has been frozen, even if it has been thawed. Do not shake SKYRIZI Pen.Keep the SKYRIZI Pen and sharps disposal container out of the reach of children. Call your healthcare provider or (866) SKYRIZI or (866) 759-7494 or go to www.SKYRIZI.com if you need help or do not know how to proceed.Questions About Using the SKYRIZI PenQ. What if need help on how to inject SKYRIZI Pen A. Call your healthcare provider or (866) SKYRIZI or (866) 759-7494 if you need help.Q. have removed the dark gray cap and pressed the green activator button. Why is my injection not starting A. The green activator button will not start the injection unless the white needle sleeve is pressed firmly against the injection site.Q. How do know when the injection is complete A. The injection is complete if the SKYRIZI Pen makes second click or the yellow indicator fills the inspection window. This takes up to 15 seconds.Q. What should do if there are more than few drops of liquid on the injection site A. Call (866) SKYRIZI or (866) 759-7494 for help.Q. What should do with the used SKYRIZI Pen after my injection A. Throw away (dispose of) the used SKYRIZI Pen in sharps disposal container right after use. Do not throw away in your household trash.For more information, see Used SKYRIZI Pen Disposal section.Call (866) SKYRIZI or (866) 759-7494 or go to www.SKYRIZI.com for help with your injection.To help remember when to inject, mark your calendar with the date you give your SKYRIZI injection.Keep the SKYRIZI Pen and sharps disposal container out of the reach of children. Call your healthcare provider or (866) SKYRIZI or (866) 759-7494 if you need help or have questions about the use of SKYRIZI.Used SKYRIZI Pen DisposalIf you do not have sharps disposal container, you may use household container that is:made of heavy-duty plastic, can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used SKYRIZI Pens.For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: www.fda.gov/safesharpsdisposal.Do not recycle your used sharps disposal container.Manufactured by: AbbVie Inc., North Chicago, IL 60064, U.S.A. US License Number 1889SKYRIZI and its design are trademarks of AbbVie Biotechnology Ltd.(C) 2026 AbbVie. All rights reserved.20101613 This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 6/2026. Store SKYRIZI Pen in the refrigerator between 36F to 46F (2C to 8C). Keep SKYRIZI Pen in the original carton to protect from light until you are ready to use. Before injecting, take the SKYRIZI Pen carton out of the refrigerator. Leave the carton at room temperature and out of direct sunlight for 30 to 90 minutes.. The liquid in the inspection window should look clear to yellow and may contain tiny white or clear particles. Do not use SKYRIZI Pen if the liquid is discolored, cloudy or contains flakes or large particles. Do not use SKYRIZI Pen if the expiration date (EXP) has passed. Do not use SKYRIZI Pen if the liquid has been frozen, even if it has been thawed. Do not shake SKYRIZI Pen. Do not use if the SKYRIZI Pen has been dropped or damaged. Do not use SKYRIZI Pen if carton perforations are broken. Return product to pharmacy.. Do not remove the dark gray cap until right before injection. SKYRIZI Pen is not made with natural rubber latex.. Do not remove the SKYRIZI Pen from the carton while allowing SKYRIZI to reach room temperature. Do not warm SKYRIZI Pen in any other way. For example, do not warm it in microwave or in hot water. Do not use the SKYRIZI Pen if the liquid has been frozen, even if it has been thawed.. single-dose SKYRIZI Pen (included) 1 alcohol swab (not included) 1 cotton ball or gauze pad (not included) Sharps disposal container (not included). See Used SKYRIZI Pen Disposal for information on how to throw away (dispose of) used SKYRIZI Pens. on the front of your left thigh or right thigh or your abdomen (belly) at least inches from your navel (belly button). Do not touch or blow on the injection site after it is cleaned. Allow the skin to dry before injecting. Do not inject through clothes. Do not inject into skin that is sore, bruised, red, hard, scarred, has stretch marks, or areas with psoriasis.. Pull the dark gray cap straight off.. Throw the dark gray cap away.. It is normal to see or more bubbles in the liquid. The liquid should look clear to yellow and may contain tiny white or clear particles. Do not use if the liquid is discolored, cloudy or contains flakes or large particles.. The SKYRIZI Pen will activate only if the white needle sleeve is pressed down against the injection site before pressing the green activator button.. The first loud click means the start of the injection.. the SKYRIZI Pen has made second click or the yellow indicator has filled the inspection window Do not rub the injection site. Slight bleeding at the injection site is normal.. Before injecting, take the SKYRIZI Pen carton out of the refrigerator. Leave the carton at room temperature and out of direct sunlight for 30 to 90 minutes. The liquid in the inspection window should look clear to yellow and may contain tiny white or clear particles. Do not use SKYRIZI Pen if the liquid is discolored, cloudy or contains flakes or large particles. Do not use SKYRIZI Pen if the expiration date (EXP) has passed. Do not use if the SKYRIZI Pen has been dropped or damaged. Do not use SKYRIZI Pen if carton perforations are broken. Return product to pharmacy. Do not remove the dark gray cap until right before injection. SKYRIZI Pen is not made with natural rubber latex.. Store SKYRIZI Pen in the refrigerator between 36F to 46F (2C to 8C). Keep SKYRIZI Pen in the original carton to protect from light until you are ready to use. Do not use SKYRIZI Pen if the liquid has been frozen, even if it has been thawed. Do not shake SKYRIZI Pen.. made of heavy-duty plastic, can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.. SKYRIZI Single-Dose Pen. Step 1. Step 2. Step 3. Step 4. Step 5. Step 6. Step 7. Step 8. Step 9. Month.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to risankizumab-rzaa are unknown. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for SKYRIZI and any potential adverse effects on the breastfed infant from SKYRIZI or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Risankizumab-rzaa is humanized IgG1 monoclonal antibody that selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is naturally occurring cytokine that is involved in inflammatory and immune responses. Risankizumab-rzaa inhibits the release of pro-inflammatory cytokines and chemokines.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenicity and mutagenicity studies have not been conducted with SKYRIZI. No effects on male fertility parameters were observed in sexually mature male cynomolgus monkeys dosed weekly for 26 weeks with 50 mg/kg risankizumab-rzaa at times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and 39 times the exposure in humans administered the maximum recommended maintenance dose (360 mg).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

NDC 0074-2100-01One mL Single-Dose Prefilled PenSkyrizi(R) PEN 150 mg/mLrisankizumab-rzaa Injection FOR SUBCUTANEOUS USE ONLYReturn to pharmacy if carton perforations are broken.ATTENTION PHARMACIST:Each patient is required to receive the enclosed Medication Guide.The entire carton is to be dispensed as unit.www.SKYRIZI.comRx onlyabbvie. NDC 0074-2100-01One mL Single-Dose Prefilled PenSkyrizi(R) PEN 150 mg/mLrisankizumab-rzaa Injection FOR SUBCUTANEOUS USE ONLYReturn to pharmacy if carton perforations are broken.ATTENTION PHARMACIST:Each patient is required to receive the enclosed Medication Guide.This entire carton is dispensed as unit.www.SKYRIZI.comRx onlyabbvie.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Moderate-to-Severe Plaque Psoriasis The safety and effectiveness of SKYRIZI for the treatment of moderate-to-severe plaque psoriasis have been established in pediatric patients years of age and older who are candidates for systemic therapy or phototherapy. Use of SKYRIZI for this indication is supported by evidence from four-part trial in total of 137 pediatric subjects years of age and older with moderate-to-severe plaque psoriasis. In addition to two lead-in pharmacokinetic cohorts, the trial also included randomized, efficacy assessor-blinded, active treatment-controlled cohort that enrolled 82 pediatric subjects 12 years of age and older and single-arm, open-label cohort that enrolled 30 pediatric subjects to less than 12 years of age [see Adverse Reactions 6.1 ), Clinical Pharmacology 12.3 ), and Clinical Studies 14.1 )]. The safety and effectiveness of SKYRIZI have not been established in pediatric patients younger than years of age with moderate-to-severe plaque psoriasis.Active Psoriatic ArthritisThe safety and effectiveness of SKYRIZI for the treatment of psoriatic arthritis have been established in pediatric patients years of age and older.Use of SKYRIZI for this indication is supported by evidence from well-controlled studies of SKYRIZI in adults with psoriatic arthritis, pharmacokinetic data from adult patients with psoriatic arthritis or plaque psoriasis, and pharmacokinetic, safety, and immunogenicity data from pediatric patients with moderate-to-severe plaque psoriasis [see dverse Reactions 6.1 ), Clinical Pharmacology 12.3 12.6 ), and Clinical Studies 14.2 ]. Risankizumab exposures in pediatric patients with psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with psoriatic arthritis based on population pharmacokinetic modeling and simulation. The safety and effectiveness of SKYRIZI have not been established in pediatric patients younger than years of age with psoriatic arthritis.Crohns Disease and Ulcerative ColitisThe safety and effectiveness of SKYRIZI have not been established in pediatric patients with Crohns disease or ulcerative colitis.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. No formal pharmacodynamics studies have been conducted with risankizumab-rzaa.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Risankizumab-rzaa plasma concentrations, after single dose administration increased dose proportionally from 18 mg to 360 mg when administered subcutaneously (0.12 to 2.4 times the lowest recommended dose and 0.05 to times the highest recommended dose) and from 200 mg to 1,800 mg when administered as an up to 3-hour intravenous infusion (0.2 to times the recommended dose) in healthy subjects. In subjects with plaque psoriasis treated with 150 mg subcutaneously at Weeks 0, 4, and every 12 weeks thereafter, steady-state peak concentration (Cmax) and trough concentration (Ctrough) are estimated to be 12 mcg/mL and mcg/mL, respectively. With the same subcutaneous dosing regimen, the pharmacokinetics of risankizumab-rzaa in subjects with psoriatic arthritis were similar to that in subjects with plaque psoriasis.In subjects with Crohns disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48.In subjects with ulcerative colitis treated with 1,200 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every weeks thereafter, the median Cmax and Ctrough are estimated to be 350 and 87.7 mcg/mL, respectively, during the induction period (Weeks 8-12); and the steady state median Cmax and Ctrough are estimated to be 19.6 and 4.64 ug/mL, respectively, for 180 mg or 39.2 mcg/mL and 9.29 mcg/mL, respectively, for 360 mg, during the maintenance period (Weeks 40-48).Based on population pharmacokinetic analyses, the pharmacokinetics of risankizumab-rzaa in subjects with ulcerative colitis was generally similar to that in subjects with Crohns disease.AbsorptionThe absolute bioavailability of risankizumab-rzaa was estimated to be 74 to 89% following subcutaneous injection. In healthy subjects, following administration of single subcutaneous dose, Cmax was reached by to 14 days. DistributionThe estimated steady-state volume of distribution (inter-subject CV%) was 11.2 (34%) in subjects with plaque psoriasis, and 7.68 (64%) in subjects with Crohns disease. EliminationThe estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and 0.30 L/day (34%) and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohns disease, respectively. MetabolismThe metabolic pathway of risankizumab-rzaa has not been characterized. As humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in manner similar to endogenous IgG. Specific PopulationsPediatric PatientsPlaque Psoriasis: Risankizumab-rzaa exposures in pediatric subjects years of age and older with plaque psoriasis receiving weight-based dosing regimens were consistent with those in adults. At the recommended dosing regimens evaluated in these subjects, estimated median steady-state peak and trough plasma concentrations were 15.7 and 2.3 mcg/mL, respectively, in subjects weighing less than 40 kg, and 11.1 and 1.6 mcg/mL, respectively, in subjects weighing 40 kg or greater. Psoriatic Arthritis: Risankizumab exposures in patients years of age and older with active psoriatic arthritis at the recommended pediatric dosage are predicted to be comparable to those observed in adult patients with psoriatic arthritis based on population pharmacokinetic modeling simulation.Geriatric PatientsRisankizumab-rzaa exposures (Ctrough) in geriatric patients (>=65 years) are comparable to those in younger adult patients within each indication. No studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab-rzaa. Body WeightRisankizumab-rzaa clearance and volume of distribution increase and plasma concentrations decrease as body weight increases; however, no dose adjustment is recommended based on body weight in adult patients. Drug Interaction StudiesCytochrome P450 SubstratesNo clinically significant changes in exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate), or midazolam (CYP3A substrate) were observed when used concomitantly with risankizumab-rzaa in subjects with plaque psoriasis (risankizumab-rzaa 150 mg administered subcutaneously at Weeks 0, 4, 8, and 12) and subjects with Crohns disease or ulcerative colitis (risankizumab-rzaa 1,800 mg administered intravenously at Weeks 0, 4, and 8, i.e., times and 1.5 times the recommended dose for Crohns disease and ulcerative colitis, respectively). Plaque Psoriasis: Risankizumab-rzaa exposures in pediatric subjects years of age and older with plaque psoriasis receiving weight-based dosing regimens were consistent with those in adults. At the recommended dosing regimens evaluated in these subjects, estimated median steady-state peak and trough plasma concentrations were 15.7 and 2.3 mcg/mL, respectively, in subjects weighing less than 40 kg, and 11.1 and 1.6 mcg/mL, respectively, in subjects weighing 40 kg or greater. Psoriatic Arthritis: Risankizumab exposures in patients years of age and older with active psoriatic arthritis at the recommended pediatric dosage are predicted to be comparable to those observed in adult patients with psoriatic arthritis based on population pharmacokinetic modeling simulation.

POSTMARKETING EXPERIENCE SECTION.

6.2 Postmarketing Experience. The following adverse reactions have been reported during post-approval of SKYRIZI. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to SKYRIZI exposure:Skin and subcutaneous tissue disorders: eczema and rash Skin and subcutaneous tissue disorders: eczema and rash.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with SKYRIZI. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com.Risk SummaryAvailable pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and SKYRIZI may cause immunosuppression in the in utero-exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease (see Clinical Considerations). In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of or 50 mg/kg risankizumab-rzaa once weekly during the period of organogenesis up to parturition. Increased fetal/infant loss was noted in pregnant monkeys at the 50 mg/kg dose (see Data). The 50 mg/kg dose in pregnant monkeys resulted in approximately times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and 32 times the exposure (AUC) to the maximum recommended maintenance dose (360 mg). No risankizumab-rzaa-related effects on functional or immunological development were observed in infant monkeys from birth through months of age. The clinical significance of these findings for humans is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal riskPublished data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth.Fetal/Neonatal adverse reactionsTransport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, SKYRIZI may be present in infants exposed in utero. The potential clinical impact of risankizumab exposure in infants exposed in utero should be considered.DataAnimal DataAn enhanced pre- and post-natal developmental toxicity study was conducted in cynomolgus monkeys. Pregnant cynomolgus monkeys were administered weekly subcutaneous doses of risankizumab-rzaa of or 50 mg/kg from gestation day 20 to parturition, and the cynomolgus monkeys (mother and infants) were monitored for months after delivery. No maternal toxicity was noted in this study. There were no treatment-related effects on growth and development, malformations, developmental immunotoxicology, or neurobehavioral development. However, dose-dependent increase in fetal/infant loss was noted in the risankizumab-rzaa-treated groups (32% and 43% in the mg/kg and 50 mg/kg groups, respectively) compared with the vehicle control group (19%). The increased fetal/infant loss in the 50 mg/kg group was considered to be related to risankizumab-rzaa treatment. The no-observed adverse effect level (NOAEL) for maternal toxicity was identified as 50 mg/kg, and the NOAEL for developmental toxicity was identified as mg/kg. The mg/kg dose in pregnant monkeys resulted in approximately 0.6 times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and times the exposure (AUC) in humans administered the maximum recommended maintenance dose (360 mg). In the infants, mean serum concentrations increased in dose-dependent manner and were approximately 17%-86% of the respective maternal concentrations. Following delivery, most adult female cynomolgus monkeys and all infants from the risankizumab-rzaa-treated groups had measurable serum concentrations of risankizumab-rzaa up to 91 days postpartum. Serum concentrations were below detectable levels at 180 days postpartum.

RECENT MAJOR CHANGES SECTION.

Indications and Usage (1.1, 1.2)6/2026Dosage and Administration (2.2, 2.3, 2.4, 2.5, 2.8)6/2026.

SPL MEDGUIDE SECTION.

Medication GuideSKYRIZI(R) (sky-RIZZ-ee)(risankizumab-rzaa)injection, for subcutaneous or intravenous useWhat is the most important information should know about SKYRIZI SKYRIZI may cause serious side effects, including:Serious allergic reactions. Stop using SKYRIZI and get emergency medical help right away if you get any of the following symptoms of serious allergic reaction: fainting, dizziness, feeling lightheaded (low blood pressure) chest tightness swelling of your face, eyelids, lips, mouth, tongue, or throat skin rash, hives trouble breathing or throat tightness itchingInfections. SKYRIZI may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with SKYRIZI and may treat you for TB before you begin treatment with SKYRIZI if you have history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with SKYRIZI. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: fever, sweats, or chills muscle aches weight loss cough warm, red, or painful skin or sores on your body different from your psoriasis diarrhea or stomach pain shortness of breath burning when you urinate or urinating more often than normal blood in your mucus(phlegm)See What are the possible side effects of SKYRIZI for more information about side effects. What is SKYRIZISKYRIZI is prescription medicine used to treat:moderate to severe plaque psoriasis in adults and children years of age and older who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy). active psoriatic arthritis in adults and children years of age and older. moderate to severe Crohns disease in adults. moderate to severe ulcerative colitis in adults.It is not known if SKYRIZI is safe and effective in children under years of age with moderate to severe plaque psoriasis or active psoriatic arthritis.It is not known if SKYRIZI is safe and effective in children with Crohns disease or ulcerative colitis. Who should not use SKYRIZIDo not use SKYRIZI if you are allergic to risankizumab-rzaa or any of the ingredients in SKYRIZI. See the end of this Medication Guide for complete list of ingredients in SKYRIZI.Before using SKYRIZI, tell your healthcare provider about all of your medical conditions, including if you:have any of the conditions or symptoms listed in the section What is the most important information should know about SKYRIZI have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). Medicines that interact with the immune system may increase your risk of getting an infection after receiving live vaccines. You should avoid receiving live vaccines right before, during, or right after treatment with SKYRIZI. Tell your healthcare provider that you are taking SKYRIZI before receiving vaccine. are pregnant or plan to become pregnant. It is not known if SKYRIZI can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if SKYRIZI passes into your breast milk. If you become pregnant while taking SKYRIZI, you are encouraged to enroll in the Pregnancy Registry. The purpose of the pregnancy registry is to collect information about the health of you and your baby. Talk to your healthcare provider or call 1-877-302-2161 to enroll in this registry.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should use SKYRIZISee the detailed Instructions for Use that comes with SKYRIZI for information on how to prepare and inject dose of SKYRIZI, and how to properly throw away (dispose of) used SKYRIZI prefilled pen, prefilled syringe, or prefilled cartridge with on-body injector. Use SKYRIZI exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you how much SKYRIZI is right for you and how often you should receive it. Before self-injecting with SKYRIZI prefilled pen, prefilled syringe, or prefilled cartridge with on-body injector, your healthcare provider should show you how to inject SKYRIZI. For children years of age and older:In children 10 years of age and older, it is recommended that SKYRIZI prefilled pen or prefilled syringe be given by an adult or with an adult watching (supervision). In children years to less than 10 years of age, SKYRIZI should be given by an adult. If you miss your SKYRIZI dose, inject dose as soon as you remember. Then, take your next dose at your regular scheduled time. Call your healthcare provider if you are not sure what to do. If you inject more SKYRIZI than prescribed, call your healthcare provider right away.Adults and children years of age and older with moderate to severe plaque psoriasis or active psoriatic arthritis will receive SKYRIZI as an injection under the skin (subcutaneous injection) using the prefilled pen or prefilled syringe.Adults with moderately to severely active Crohns disease or moderately to severely active ulcerative colitis will receive their starter doses with SKYRIZI through vein in the arm (intravenous infusion) in healthcare facility by healthcare provider. After completing the starter doses, patients will receive SKYRIZI as or more injections under the skin (subcutaneous injection) using the prefilled cartridge with on-body injector or prefilled syringe.What are the possible side effects of SKYRIZISKYRIZI may cause serious side effects including:See What is the most important information should know about SKYRIZILiver problems may happen while being treated for Crohns disease or ulcerative colitis. person with Crohns disease who received SKYRIZI by intravenous infusion (through vein in the arm) developed changes in liver blood tests with rash that led to hospitalization. Your healthcare provider will do blood tests to check your liver before, during, and at least up to 12 weeks of treatment with SKYRIZI. Your healthcare provider may stop treatment with SKYRIZI if you develop liver problems. Tell your healthcare provider right away if you notice any of the following symptoms:unexplained rash nauseavomiting stomach (abdominal) paintiredness (fatigue) loss of appetiteyellowing of the skin and eyes (jaundice) dark urineThe most common side effects of SKYRIZI in people treated for Crohns disease and ulcerative colitis include:upper respiratory infections headache joint painstomach (abdominal) pain injection site reactions low red blood cells (anemia)fever back pain urinary tract infection rashThe most common side effects of SKYRIZI in people treated for plaque psoriasis and psoriatic arthritis include:upper respiratory infections headachefeeling tired injection site reactionsfungal skin infectionsThese are not all the possible side effects of SKYRIZI.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store SKYRIZIStore SKYRIZI in the refrigerator between 36F to 46F (2C to 8C). Do not freeze SKYRIZI. Do not shake SKYRIZI. Keep SKYRIZI in the original carton to protect it from light. SKYRIZI is not made with natural rubber latex.Keep SKYRIZI and all medicines out of the reach of children.General information about the safe and effective use of SKYRIZI.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use SKYRIZI for condition for which it was not prescribed. Do not give SKYRIZI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about SKYRIZI that is written for health professionals. What are the ingredients in SKYRIZIActive ingredient: risankizumab-rzaa. SKYRIZI 90 mg/mL prefilled syringe inactive ingredient s: polysorbate 20, sodium succinate, sorbitol, succinic acid, and Water for Injection, USP. SKYRIZI 55 mg/0.37 mL prefilled syringe, 150 mg/mL prefilled pen or prefilled syringe 180 mg/1.2 mL prefilled syringe or prefilled cartridge 360 mg/2.4 mL prefilled cartridge and 600 mg/ 10 mL vial nactive ingredients: glacial acetic acid, polysorbate 20, sodium acetate, trehalose, and Water for Injection, USP. Manufactured by: AbbVie Inc., North Chicago, IL 60064, U.S.A.US License Number 1889SKYRIZI and its design are trademarks of AbbVie Biotechnology Ltd.(C) 2026 AbbVie. All rights reserved.For more information, call 1-866-SKYRIZI (1-866-759-7494) or go to www.SKYRIZI.com. This Medication Guide has been approved by the U.S. Food and Drug Administration20101630 Revised: 6/2026. moderate to severe plaque psoriasis in adults and children years of age and older who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy). active psoriatic arthritis in adults and children years of age and older. moderate to severe Crohns disease in adults. moderate to severe ulcerative colitis in adults.It is not known if SKYRIZI is safe and effective in children under years of age with moderate to severe plaque psoriasis or active psoriatic arthritis.. have any of the conditions or symptoms listed in the section What is the most important information should know about SKYRIZI have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). Medicines that interact with the immune system may increase your risk of getting an infection after receiving live vaccines. You should avoid receiving live vaccines right before, during, or right after treatment with SKYRIZI. Tell your healthcare provider that you are taking SKYRIZI before receiving vaccine. are pregnant or plan to become pregnant. It is not known if SKYRIZI can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if SKYRIZI passes into your breast milk. If you become pregnant while taking SKYRIZI, you are encouraged to enroll in the Pregnancy Registry. The purpose of the pregnancy registry is to collect information about the health of you and your baby. Talk to your healthcare provider or call 1-877-302-2161 to enroll in this registry.. Use SKYRIZI exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you how much SKYRIZI is right for you and how often you should receive it. Before self-injecting with SKYRIZI prefilled pen, prefilled syringe, or prefilled cartridge with on-body injector, your healthcare provider should show you how to inject SKYRIZI. For children years of age and older:In children 10 years of age and older, it is recommended that SKYRIZI prefilled pen or prefilled syringe be given by an adult or with an adult watching (supervision). In children years to less than 10 years of age, SKYRIZI should be given by an adult. In children 10 years of age and older, it is recommended that SKYRIZI prefilled pen or prefilled syringe be given by an adult or with an adult watching (supervision). In children years to less than 10 years of age, SKYRIZI should be given by an adult.. If you miss your SKYRIZI dose, inject dose as soon as you remember. Then, take your next dose at your regular scheduled time. Call your healthcare provider if you are not sure what to do. If you inject more SKYRIZI than prescribed, call your healthcare provider right away.. See What is the most important information should know about SKYRIZI. Liver problems may happen while being treated for Crohns disease or ulcerative colitis. person with Crohns disease who received SKYRIZI by intravenous infusion (through vein in the arm) developed changes in liver blood tests with rash that led to hospitalization. Your healthcare provider will do blood tests to check your liver before, during, and at least up to 12 weeks of treatment with SKYRIZI. Your healthcare provider may stop treatment with SKYRIZI if you develop liver problems. Tell your healthcare provider right away if you notice any of the following symptoms:. unexplained rash nausea. vomiting stomach (abdominal) pain. tiredness (fatigue) loss of appetite. yellowing of the skin and eyes (jaundice) dark urine. upper respiratory infections headache joint pain. stomach (abdominal) pain injection site reactions low red blood cells (anemia). fever back pain urinary tract infection rash. upper respiratory infections headache. feeling tired injection site reactions. fungal skin infections. Store SKYRIZI in the refrigerator between 36F to 46F (2C to 8C). Do not freeze SKYRIZI. Do not shake SKYRIZI. Keep SKYRIZI in the original carton to protect it from light. SKYRIZI is not made with natural rubber latex.

SPL UNCLASSIFIED SECTION.

1.1 Plaque Psoriasis. SKYRIZI(R) is indicated for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients years of age and older who are candidates for systemic therapy or phototherapy.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with SKYRIZI. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com.Risk SummaryAvailable pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and SKYRIZI may cause immunosuppression in the in utero-exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease (see Clinical Considerations). In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of or 50 mg/kg risankizumab-rzaa once weekly during the period of organogenesis up to parturition. Increased fetal/infant loss was noted in pregnant monkeys at the 50 mg/kg dose (see Data). The 50 mg/kg dose in pregnant monkeys resulted in approximately times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and 32 times the exposure (AUC) to the maximum recommended maintenance dose (360 mg). No risankizumab-rzaa-related effects on functional or immunological development were observed in infant monkeys from birth through months of age. The clinical significance of these findings for humans is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal riskPublished data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth.Fetal/Neonatal adverse reactionsTransport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Therefore, SKYRIZI may be present in infants exposed in utero. The potential clinical impact of risankizumab exposure in infants exposed in utero should be considered.DataAnimal DataAn enhanced pre- and post-natal developmental toxicity study was conducted in cynomolgus monkeys. Pregnant cynomolgus monkeys were administered weekly subcutaneous doses of risankizumab-rzaa of or 50 mg/kg from gestation day 20 to parturition, and the cynomolgus monkeys (mother and infants) were monitored for months after delivery. No maternal toxicity was noted in this study. There were no treatment-related effects on growth and development, malformations, developmental immunotoxicology, or neurobehavioral development. However, dose-dependent increase in fetal/infant loss was noted in the risankizumab-rzaa-treated groups (32% and 43% in the mg/kg and 50 mg/kg groups, respectively) compared with the vehicle control group (19%). The increased fetal/infant loss in the 50 mg/kg group was considered to be related to risankizumab-rzaa treatment. The no-observed adverse effect level (NOAEL) for maternal toxicity was identified as 50 mg/kg, and the NOAEL for developmental toxicity was identified as mg/kg. The mg/kg dose in pregnant monkeys resulted in approximately 0.6 times the exposure (AUC) in humans administered the maximum recommended induction dose (1,200 mg) and times the exposure (AUC) in humans administered the maximum recommended maintenance dose (360 mg). In the infants, mean serum concentrations increased in dose-dependent manner and were approximately 17%-86% of the respective maternal concentrations. Following delivery, most adult female cynomolgus monkeys and all infants from the risankizumab-rzaa-treated groups had measurable serum concentrations of risankizumab-rzaa up to 91 days postpartum. Serum concentrations were below detectable levels at 180 days postpartum. 8.2 Lactation. Risk SummaryThere are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to risankizumab-rzaa are unknown. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for SKYRIZI and any potential adverse effects on the breastfed infant from SKYRIZI or from the underlying maternal condition. 8.4 Pediatric Use. Moderate-to-Severe Plaque Psoriasis The safety and effectiveness of SKYRIZI for the treatment of moderate-to-severe plaque psoriasis have been established in pediatric patients years of age and older who are candidates for systemic therapy or phototherapy. Use of SKYRIZI for this indication is supported by evidence from four-part trial in total of 137 pediatric subjects years of age and older with moderate-to-severe plaque psoriasis. In addition to two lead-in pharmacokinetic cohorts, the trial also included randomized, efficacy assessor-blinded, active treatment-controlled cohort that enrolled 82 pediatric subjects 12 years of age and older and single-arm, open-label cohort that enrolled 30 pediatric subjects to less than 12 years of age [see Adverse Reactions 6.1 ), Clinical Pharmacology 12.3 ), and Clinical Studies 14.1 )]. The safety and effectiveness of SKYRIZI have not been established in pediatric patients younger than years of age with moderate-to-severe plaque psoriasis.Active Psoriatic ArthritisThe safety and effectiveness of SKYRIZI for the treatment of psoriatic arthritis have been established in pediatric patients years of age and older.Use of SKYRIZI for this indication is supported by evidence from well-controlled studies of SKYRIZI in adults with psoriatic arthritis, pharmacokinetic data from adult patients with psoriatic arthritis or plaque psoriasis, and pharmacokinetic, safety, and immunogenicity data from pediatric patients with moderate-to-severe plaque psoriasis [see dverse Reactions 6.1 ), Clinical Pharmacology 12.3 12.6 ), and Clinical Studies 14.2 ]. Risankizumab exposures in pediatric patients with psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with psoriatic arthritis based on population pharmacokinetic modeling and simulation. The safety and effectiveness of SKYRIZI have not been established in pediatric patients younger than years of age with psoriatic arthritis.Crohns Disease and Ulcerative ColitisThe safety and effectiveness of SKYRIZI have not been established in pediatric patients with Crohns disease or ulcerative colitis.. 8.5 Geriatric Use. Of the 6,862 subjects exposed to SKYRIZI, total of 664 were 65 years and older (243 subjects with plaque psoriasis, 246 subjects with psoriatic arthritis, 72 subjects with Crohns disease and 103 subjects with ulcerative colitis), and 71 subjects were 75 years and older. Clinical studies of SKYRIZI, within each indication, did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed based on age [see Clinical Pharmacology 12.3 )].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur. (5.1) Infections: SKYRIZI may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, do not administer SKYRIZI until the infection resolves. (5.2) Tuberculosis (TB): Evaluate for TB prior to initiating treatment with SKYRIZI. (5.3) Hepatotoxicity: Drug-induced liver injury during induction treatment of inflammatory bowel disease has been reported. Monitor liver enzymes and bilirubin levels at baseline and, during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management. (5.4) Immunizations: Avoid use of live vaccines. (5.5) Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur. (5.1) Infections: SKYRIZI may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, do not administer SKYRIZI until the infection resolves. (5.2) Tuberculosis (TB): Evaluate for TB prior to initiating treatment with SKYRIZI. (5.3) Hepatotoxicity: Drug-induced liver injury during induction treatment of inflammatory bowel disease has been reported. Monitor liver enzymes and bilirubin levels at baseline and, during induction, up to at least 12 weeks of treatment. Monitor thereafter according to routine patient management. (5.4) Immunizations: Avoid use of live vaccines. (5.5) 5.1 Hypersensitivity Reactions. Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of SKYRIZI. If serious hypersensitivity reaction occurs, discontinue SKYRIZI and initiate appropriate therapy immediately [see Adverse Reactions 6.1 )]. 5.2 Infections. SKYRIZI may increase the risk of infections [see Adverse Reactions 6.1 )]. Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with chronic infection or history of recurrent infection, consider the risks and benefits prior to prescribing SKYRIZI. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer SKYRIZI until the infection resolves. 5.3 Tuberculosis. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI. Across the Phase psoriasis clinical studies, of the 72 subjects with latent TB who were concurrently treated with SKYRIZI and appropriate TB prophylaxis during the studies, none developed active TB during the mean follow-up of 61 weeks on SKYRIZI. Two subjects taking isoniazid for treatment of latent TB discontinued treatment due to liver injury. Of the 31 subjects from the PsO-3 study with latent TB who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on SKYRIZI. Consider anti-TB therapy prior to initiating SKYRIZI in patients with past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SKYRIZI treatment. Do not administer SKYRIZI to patients with active TB. 5.4 Hepatotoxicity A serious adverse reaction of drug-induced liver injury in conjunction with rash that required hospitalization was reported in patient with Crohns disease (ALT 54x ULN, AST 30x ULN, and total bilirubin 2.2x ULN) following two 600 mg intravenous doses of SKYRIZI. The liver test abnormalities resolved following administration of steroids. SKYRIZI was subsequently discontinued.For the treatment of Crohns disease and ulcerative colitis, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. 5.5 Immunizations. Avoid use of live vaccines in patients treated with SKYRIZI. Drugs that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with SKYRIZI, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or inactive vaccines.