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

factors.3 Potential patient risk factors for adverse reactions can include race, gender, age, concomitant illness, concomitant medications, psychologic factors, and comorbidities. Similarly, numerous factors may be associated with the molecule or injection, such as molecular weight, volume, speed of injection, and excipients. For ixekizumab, the pH is 5.3–6.1,12 and its excipients were balanced to support chemical and structural stability while minimizing irritation (data on file). Overall, given the multitude of variables, the exact pathogenesis of injection-site reactions, including injection pain, is not known for ixekizumab.One difference between the ixekizumab clinical trials and the experience of patients postmarketing is that the clinical trials, and hence the data in this report, were primarily conducted with self-administration using a prefilled syringe in contrast to increased use of the autoinjector device postmarketing. Ixekizumab should be kept at room temperature for 30 minutes before administration and the cap should not be removed. The autoinjector “instructions for use” should be reviewed by all patients, even those with prior experience with biologic injections, due to the difference in the technique for proper administration of the ixekizumab autoinjector. Some patients may find that they prefer the control of using the prefilled syringe and may benefit from this option if they are uncomfortable with the autoinjector.This report includes one of the largest cohorts of patients being treated with an IL-17A antagonist for the treatment of moderate-to-severe psoriasis. When interpreting the results, it should be considered that the placebo-controlled periods of the UNCOVER studies are limited to 12 weeks. Additionally, solicited injection-site reactions were collected using a standardized questionnaire only if patients reported an event associated with the injection; therefore, minor events might be underreported. In the analyses described within, the most common term reported was “nonspecified” injection-site reaction. As a result, specific forms of injection-site reactions might be underreported. Other factors that may impact the reporting of injection-site reactions may be documentation errors, potentially related to investigator fatigue as well as a patient’s recall bias or reservation to report to the investigator. This report is limited to data collected in clinical trials. Based on limited preliminary postmarketing data, the presented profile of injection-site reactions is consistent with real-world use, although the magnitude of postmarketing reporting could be different.In conclusion, previously reported safety data supports an overall favorable safety profile of ixekizumab,5,7-10 including injection-site reactions as among the commonly reported adverse events. The injection-site reactions reported with ixekizumab treatment have been tolerable and clinically manageable, and the incidence decreases over time. These data may help clinicians counseling patients experiencing such reactions. Clinicians and patients should balance the risk of potential injection-site reactions with the efficacy benefits of the drug.

DISCLOSURES

NH Shear has acted as a paid consultant for AbbVie, Amgen, Celgene, Janssen, Leo Pharma, Eli Lilly and Company, Novartis, and Valeant.C Paul has been investigator or consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermira, Inc., Eli Lilly and Company, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi Genzyme, and UCB Pharma.A Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Inc., Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac, and as a paid speaker for Eli Lilly and Company, Janssen, Regeneron, and Sanofi Genzyme.M Gooderham has been an investigator, speaker, advisory board member, or consultant for Amgen, AbbVie, Boehringer Ingelheim, Celgene, Dermira, Inc., Eli Lilly and Company, Galderma, GlaxoSmithKline, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Roche, Regeneron, Sanofi Genzyme, Takeda, UCB, and Valeant.C Leonardi has been a consultant/advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Dermira Inc., Eli Lilly and Company, Janssen, Leo Pharma, Pfizer, Sandoz, UCB, and Vitae, has been an investigator for Actavis, AbbVie, Amgen, Boehringer Ingelheim, Celgene, Coherus, Cellceutix, Corrona, Dermira, Inc., Eli Lilly and Company, Galderma, Glenmark, Janssen, Leo Pharma, Merck, Novartis, Novella, Pfizer, Sandoz, Stiefel, Wyeth, and has been a speakers bureau participant for AbbVie, Celgene, Novartis, and Eli Lilly and Company.K Reich has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly and Company, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB, and Xenoport.M Ohtsuki has received honoraria as consultant and/or advisory board member and acted as paid speaker and/or participated in clinical trials sponsored by AbbVie, Boehringer Ingelheim, Celgene, Eisai, Janssen, Kyowa-Kirin, Leo Pharma, Eli Lilly and Company, Maruho, Novartis, Pfizer, and Mitsubishi-Tanabe.H Torisu-Itakura is an employee and stockholder of Eli Lilly Japan KK.B Pangallo, W Xu, S Ball, T Ridenour, N Agada, L Mallbris are employees and stockholders of Eli Lilly and Company.Funding for each study was provided by Eli Lilly and Company.IRB approval was obtained from each study site.

ACKNOWLEDGMENTS

The authors would like to thank Kelly Guerrettaz, MA, an employee of INC Research/inVentiv Health (Raleigh, NC), funded by Eli Lilly and Company, for her assistance with manuscript development.

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AUTHOR CORRESPONDENCE

Neil H. Shear MD FRCPC Neil.Shear@sunnybrook.ca