SKYRIZI is an interleukin-23 antagonist indicated for the treatment of: moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. ( 1.1 ) active psoriatic arthritis in adults. ( 1.2 ) moderately to severely active Crohn's disease in adults. ( 1.3 ) moderately to severely active ulcerative colitis in adults. ( 1.4 )
1.1Plaque Psoriasis
SKYRIZI ® is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
1.2Psoriatic Arthritis
SKYRIZI is indicated for the treatment of active psoriatic arthritis in adults.
1.3Crohn’s Disease
SKYRIZI is indicated for the treatment of moderately to severely active Crohn's disease in adults.
1.4Ulcerative Colitis
SKYRIZI is indicated for the treatment of moderately to severely active ulcerative colitis in adults.
Contraindications
SKYRIZI is contraindicated in patients with a 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 a history of serious hypersensitivity reaction to risankizumab-rzaa or any of the excipients ( 4 )
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.
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( 5.3 ) Hepatotoxicity in Treatment of Inflammatory Bowel Disease: Drug-induced liver injury during induction 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 ) Administration of Vaccines: Avoid use of live vaccines. ( 5.5 )
5.1Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of SKYRIZI. If a 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 a chronic infection or a 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 a 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 3 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 a 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 in Treatment of Inflammatory Bowel Disease A serious adverse reaction of drug-induced liver injury in conjunction with a rash that required hospitalization was reported in a patient with Crohn’s 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 Crohn’s 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.
5.5Administration of Vaccines
Avoid use of live vaccines in patients treated with SKYRIZI. Medications 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.
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a 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 Summary Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a 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 5 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 5 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 6 months of age.
The clinical significance of these findings for humans is unknown. All pregnancies have a 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 risk Published 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 reactions Transport 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. Data Animal Data An 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 5 or 50 mg/kg from gestation day 20 to parturition, and the cynomolgus monkeys (mother and infants) were monitored for 6 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, a dose-dependent increase in fetal/infant loss was noted in the risankizumab-rzaa-treated groups (32% and 43% in the 5 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 5 mg/kg. The 5 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 5 times the exposure (AUC) in humans administered the maximum recommended maintenance dose (360 mg).
In the infants, mean serum concentrations increased in a 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.
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 in Treatment of Inflammatory Bowel Disease [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 ) Crohn’s 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.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Plaque Psoriasis A 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 2 summarizes the adverse drug reactions that occurred at a rate of at least 1% and at a higher rate in the SKYRIZI group than the placebo group during the 16-week controlled period of pooled clinical trials. Table 2. Adverse Drug Reactions Occurring in ≥ 1% of Subjects with Plaque Psoriasis on SKYRIZI through Week 16 Adverse Drug Reactions SKYRIZI N = 1306 n (%) Placebo N = 300 n (%) Upper respiratory infections a 170 (13.0) 29 (9.7) Headache b 46 (3.5) 6 (2.0) Fatigue c 33 (2.5) 3 (1.0) Injection site reactions d 19 (1.5) 3 (1.0) Tinea infections e 15 (1.1) 1 (0.3) a Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis (including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis b Includes: headache, tension headache, sinus headache, cervicogenic headache c Includes: fatigue, asthenia d Includes: injection site bruising, erythema, extravasation, hematoma, hemorrhage, infection, inflammation, irritation, pain, pruritus, reaction, swelling, warmth e Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum, tinea infection, onychomycosis Adverse drug reactions that occurred in < 1% but > 0.1% of subjects in the SKYRIZI group and at a higher rate than in the placebo group through Week 16 were folliculitis and urticaria.
Specific Adverse Drug Reactions Infections 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 T hrough Week 52 Through 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 Area The 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 )] . Psoriatic Arthritis The overall safety profile observed in subjects with psoriatic arthritis treated with SKYRIZI is generally consistent with the safety profile in subjects with plaque psoriasis.
Additionally, in the Phase 3 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 3 placebo-controlled trials, hypersensitivity reactions reported at a 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 a subject who received SKYRIZI in the Phase 2 clinical trial. Crohn’s Disease SKYRIZI was studied up to 12 weeks in subjects with moderately to severely active Crohn’s disease in two randomized, double-blind, placebo-controlled induction trials (CD-1, CD-2) and a 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 a 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, 4 and 8. In the maintenance trial (CD-3), 297 subjects who achieved clinical response, defined as a 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 a maintenance regimen of SKYRIZI either 180 mg or 360 mg subcutaneously at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks.
Adverse reactions reported in > 3% of subjects in induction trials and at a higher rate than placebo are shown in Table 3. Table 3. Adverse Drug Reactions Reported in > 3% of Subjects with Crohn’s Disease Treated with SKYRIZI in Placebo-Controlled 12-Week Induction Trials (CD-1, CD-2, and CD-4) Adverse Drug Reactions SKYRIZI 600 mg Intravenous Infusion a N = 620 n (%) Placebo N = 432 n (%) Upper respiratory infections b 66 (10.6) 40 (9.3) Headache c 41 (6.6) 24 (5.6) Arthralgia 31 (5.0) 19 (4.4) a SKYRIZI 600 mg as an intravenous infusion at Week 0, Week 4, and Week 8. b 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 c Includes: headache, tension headache Adverse reactions reported in >3% of subjects in the maintenance trial and at a higher rate than placebo are shown in Table 4.
Table 4. Adverse Reactions Reported in >3% of Subjects with Crohn’s Disease Treated with SKYRIZI a in Placebo-Controlled 52-Week Maintenance Trial (CD-3) Adverse Drug Reactions SKYRIZI 180 mg Subcutaneous Injection N = 155 n (%) SKYRIZ
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
RISANKIZUMAB-RZAA 75MG/0.83ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
