baseline. Frequencies and 95% confidence intervals (CIs) of treatment-emergent injection-site reactions are presented for the treatment groups for the PPC, PAC, and AP analysis sets. The 95% CIs of the frequencies were calculated based on binomial distributions. Treatment comparisons for frequencies were analyzed for PPC and PAC analysis sets using the Cochran-Mantel-Haenszel test stratified by study. Frequencies of treatment-emergent injection-site reactions are also presented by race, for those with or without previous biologic experience, and for those with or without treatment-emergent antidrug antibody (TE-ADA) positive status. A TE-ADA positive patient was defined as having a post-baseline antibody titer with a ≥4-fold increase over a positive baseline antibody titer (Tier 3) or an increase from a negative baseline titer to a level of ≥1:10. Frequencies included any injection-site reaction reported within (±)14 days of a positive TE-ADA result.
RESULTS
Injection-Site Reactions During the Induction Dosing Period of the UNCOVER StudiesDuring the 12-week induction period of the phase 3 UNCOVER studies (N=3858 patients), the overall frequency of reported injection-site reactions with IXE Q2W (16.8%) was similar to those reported with etanercept administered twice weekly (16.4%; Figure 1); the frequencies with IXE Q2W and etanercept were both higher than with placebo (3.3%). Five ixekizumab-treated patients (nonspecified, n=4; erythema, n=1) and 3 etanercept-treated patients (nonspecified, n=2; hypersensitivity, n=1) discontinued due to injection-site reactions that occurred during the 12-week induction period. No patients in the placebo group discontinued due to injection-site reaction. Among injection-site reactions reported, the severities were mild (IXE Q2W: 12.3%; etanercept: 11.2%), moderate (IXE Q2W: 3.9%; etanercept: 3.7%), or severe (IXE Q2W: 0.7%; etanercept: 1.4%). The most common injection-site reactions following IXE Q2W treatment were nonspecified (10.0%), erythema (4.5%), and pain (2.4%).The median time to first onset of injection-site reactions after week 0 injections was 6.6 days with IXE Q2W. At subsequent injection weeks (weeks 2 and 4), the median time to onset of injection-site reactions decreased to 1.5 days. In general, a delay in the onset of injection-site erythema was reported. The median time to first onset of erythema was 8.3 days with IXE Q2W. The median duration of erythema was 4.0 days, although in a few outlier cases, patients reported erythema for up to 7 weeks. Typically,