Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials

February 2018 | Volume 17 | Issue 2 | Original Article | 200 | Copyright © February 2018

Neil H. Shear MD FRCPC,a Carle Paul MD PhD,b Andrew Blauvelt MD MBA,c Melinda Gooderham MD MSc FRCPC,d Craig Leonardi MD,e Kristian Reich MD PhD,f Mamitaro Ohtsuki MD PhD,g Beth Pangallo RN,h Wen Xu PhD,h Susan Ball PhD,h Terri Ridenour MBA BSN,h Hitoe Torisu-Itakura MD PhD,i Noah Agada, MD MPH,h and Lotus Mallbris MD PhDh

aSunnybrook Health Sciences Centre, Dermatology, Clinical Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada bCHU and Paul Sabatier University, Toulouse, France cOregon Medical Research Center, Portland, OR dSKIN Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, ON, Canada eSt. Louis University School of Medicine, St. Louis, MO fDermarologikum Hamburg and SCIderm Research Institute, Hamburg, Germany gJichi Medical University, Tochigi, Japan hEli Lilly and Company, Indianapolis, IN iEli Lilly Japan KK, Hyogo, Japan

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.


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,Figure1Figure2