red in 22.1% of the SKYRIZI group (90.8 events per 100subject-years) compared to 14.7% of the placebo group (56.5 events per 100 subject-years) anddid not lead to discontinuation of SKYRIZI. The rates of serious infections for the SKYRIZIgroup and the placebo group were ≤0.4%. Seriousinfections in the SKYRIZI group includedcellulitis, osteomyelitis, sepsis and herpes zoster.
In ULTIMMA-1 and ULTIMMA-2, throughWeek 52, the rate of infections (73.9 events per 100 subject-years) was similar to the rateobserved during the first 16 weeks of treatment.
Safety through Week 52
Through Week 52, no new adverse reactions were identified and the rates of the adversereactions were similar to those observed during the first 16 weeks of treatment. During thisperiod, serious infections that led to study discontinuation included pneumonia.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibodyformation is highly dependent on the sensitivity and specificity of the assay. Additionally, theobserved incidence of antibody (including neutralizing antibody) positivity in an assay may beinfluenced by several factors including assay methodology, sample handling, timing of samplecollection, concomitant medications, and underlying disease. For these reasons, comparison ofthe incidence of antibodies in the studies described below with the incidence of antibodies inother studies or to other products, including other risankizumab products, may be misleading.
By Week 52, approximately 24% (263/1079) of subjects treated with SKYRIZI at therecommended dose developed antibodies to risankizumab-rzaa. Of the subjectswhodevelopedantibodies 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% ofsubjects treated with SKYRIZI were associated with lower risankizumab-rzaa concentrations andreduced clinical response.
7 DRUG INTERACTIONS
7.1 Live Vaccinations
Avoid use of live vaccines in patients treated with SKYRIZI [see Warnings and Precautions(5.2)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Limited available data with SKYRIZI use in pregnant women are insufficient to eva luate a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. HumanIgG is known to cross the placental barrier; therefore, SKYRIZI may be transmitted from themother to the developing fetus.
In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeyswere administered subcutaneous doses of 5 and 50 mg/kg risankizumab-rzaa once weekly duringthe period of organogenesis up to parturition. At the 50 mg/kg dose [20 times the maximumrecommended human dose (MRHD); 2.5 mg/kg based on administration of a 150 mg dose to a60 kg individual], increased fetal/infant loss was noted in pregnant monkeys (see Data). Norisankizumab-rzaa-related effects on functional or immunological development were observed ininfant monkeys from birth through 6 months of age. The clinical significance of these findingsfor humans is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Theestimated background risk of major birth defects and miscarriage for the indicated population isunknown. In the U.S. general population, the estimated background risk of ma |
