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Adverse reactions reported in ≥3% of subjects treated with SKYRIZI in the maintenance study (UC-2) and at a higher rate than placebo are shown in Table 4. Table 4. Adverse Reactions Reported in ≥3% of Subjects with Ulcerative Colitis Treated with SKYRIZI a in Placebo-Controlled 52-Week Maintenance Study (UC-2)
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. Because risankizumab may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed to SKYRIZI in utero. There are insufficient data regarding infant serum levels of risankizumab at birth and the duration of persistence of risankizumab in infant serum after birth. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 5 months after birth should be considered because of the half-life of the product. 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. Lactation Risk Summary There 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 mother’s clinical need for SKYRIZI and any potential adverse effects on the breastfed infant from SKYRIZI or from the underlying maternal condition. Pediatric Use The safety and effectiveness of SKYRIZI have not been established in pediatric patients. Geriatric Use Of the 6,862 subjects exposed to SKYRIZI, a total of 664 were 65 years or older (243 subjects with plaque psoriasis, 246 subjects with psoriatic arthritis, 72 subjects with Crohn’s disease and 103 subjects with ulcerative colitis), and 71 subjects were 75 years or 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. PATIENT COUNSELING INFORMATION Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Hypersensitivity Reactions Advise patients to discontinue SKYRIZI and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions]. Infections Inform 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] . Hepatotoxicity in Treatment of Inflammatory Bowel Disease 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].
Administration of Vaccines Advise 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 a potential vaccination [see Warnings and Precautions] . Administration Instruction Instruct patients or caregivers to perform the first self-injected dose under the supervision and guidance of a qualified healthcare professional for training in preparation and administration of SKYRIZI, including choosing anatomical sites for administration, and proper subcutaneous injection technique. 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 Crohn’s disease. Instruct patients or caregivers in the technique of pen or syringe disposal. Pregnancy Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to SKYRIZI during pregnancy [see Use in Specific Populations] . Manufactured by: AbbVie Inc. North Chicago, IL 60064, USA US License Number 1889 SKYRIZI ® is a registered trademark of AbbVie Biotechnology Ltd. © 2019-2024 AbbVie Inc.
SKYRIZI 180 mg Subcutaneous Injection N = 170 n (%)
SKYRIZI 360 mg Subcutaneous Injection N = 177 n (%)
Placebo N = 173 n (%)
Adverse Drug Reactions
Arthralgia
9 (5.3) 8 (4.7) 5 (2.9) 7 (4.1)
17 (9.6)
8 (4.6) 6 (3.5) 2 (1.2)
Pyrexia
7 (4.0)
Injection site reactions b,c
5 (2.8) 1 (0.6)
Rash d 3 (1.7) a SKYRIZI 180 mg or 360 mg at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks b Includes: application site pain, injection site erythema, injection site pain, injection site pruritus, injection site reaction c 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. d Includes: rash and rash macular Specific Adverse Drug Reactions The rates of infections, serious infections, and lipid elevations in subjects with UC who received SKYRIZI compared to subjects who received placebo in the induction studies (UC-1 and UC-3) and maintenance study (UC-2) were similar to the rates in subjects with CD who received SKYRIZI compared to subjects who received placebo in the induction studies (CD-1, CD-2, and CD-4) and maintenance study (CD-3). Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products, including other risankizumab products, may be misleading. Plaque Psoriasis By Week 52, approximately 24% (263/1079) of subjects treated with SKYRIZI at the recommended dose 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. Psoriatic Arthritis By Week 28, approximately 12.1% (79/652) of 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. A 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. Crohn’s Disease By 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. Ulcerative Colitis By 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. Postmarketing Experience The following adverse reactions have been reported during post-approval of SKYRIZI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to SKYRIZI exposure: • Skin and subcutaneous tissue disorders : eczema and rash USE IN SPECIFIC POPULATIONS Pregnancy 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
Ref: 20086179 R1 Revised: June 2024 LAB-11460 MASTER
US-SKZG-241093
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Revista Puertorriqueña de Medicina y Salud Pública
Revista Puertorriqueña de Medicina y Salud Pública
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