Serious Gastrointestinal-Related Adverse Events Among Psoriasis Patients Treated With Guselkumab in VOYAGE 1 and VOYAGE 2
August 2021 | Volume 20 | Issue 8 | Original Article | 855 | Copyright © August 2021
Peter Foley MD,a Kristian Reich MD,b Andrew Blauvelt MD,c Jerry Bagel MD,d Richard G. Langley MD,e Megan Miller MPH,f Paraneedharan Ramachandran MD,f Ya Wen Yang MD,g Yaung-Kaung Shen PhD,f Yin You MS,f Mark Lebwohl MD,h Christopher E.M. Griffiths MDi
aThe University of Melbourne, St. Vincent’s Hospital Melbourne and Probity Medical Research, Skin Health Institute, Carlton, VIC, Australia;
b Center for Translational Research in Inflammatory Skin Disease, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
c Oregon Medical Research Center, Portland, OR;
d The Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ;
e Dalhousie University, Halifax, Nova Scotia, Canada;
f Janssen Research & Development, LLC, Spring House, PA;
g Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA;
h Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY;
i The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester NIHR Biomedical Research Centre, Manchester, United Kingdom
Abstract
Background: Anti-interleukin (IL)-17 biologic agents used to treat psoriasis are associated with onset/exacerbation of inflammatory bowel disease (IBD). Objectives: To determine the incidence of IBD or serious gastrointestinal-related adverse events (GI SAEs) in patients with moderate-to-severe psoriasis treated with guselkumab, an IL-23p19 inhibitor that indirectly inhibits IL-17, through 4 years in the phase 3 VOYAGE 1 and VOYAGE 2 trials. Methods: Patients were randomized to guselkumab 100 mg every-8-weeks or placebo→guselkumab (week 16), or adalimumab. In VOYAGE 1, all patients received open-label guselkumab starting at week 52. In VOYAGE 2, eligible patients were treated with guselkumab or placebo based on clinical response starting at week 28 and received open-label guselkumab starting at week 76. Cumulative incidence rates of IBD and other GI SAEs were calculated as events per 100 patient-years (PY) through week 204. IBD was defined as AEs of Crohn’s disease or ulcerative colitis. Data were summarized for all guselkumab-treated patients for years 1-4. Results: Of 1721 guselkumab-treated patients, 1612 were exposed for ≥1 year, 1545 for ≥2 years, 1454 for ≥3 years, and 661 for ≥4 years. For all patients through week 204, the cumulative rate of GI SAEs was 0.45/100PY. Event rates remained stable with longer duration of exposure, ranging from 0.36 to 0.57/100PY. No new or exacerbated cases of IBD were reported. Conclusions: No cases of IBD were observed and rates of GI SAEs were low through 4 years of treatment with guselkumab in two large trials of patients with psoriasis. J Drugs Dermatol. 2021;20(8):855-860. doi:10.36849/JDD.6216 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.
INTRODUCTION
Psoriasis is a systemic, immune-mediated, inflammatory disease manifested in the skin and associated with multiple comorbidities, including inflammatory bowel disease (IBD).1 Psoriasis and IBD share a common pathogenic link based on mutual cellular mediators (eg, T17 helper cells), inflammatory pathways, and genetic factors.2 Biologic agents targeting the interleukin (IL)-23/IL-17A signaling pathway have been used extensively to treat psoriasis. Some of these agents that target IL-17 have been associated with either new onset or exacerbation of IBD in the setting of skin disease.3-5
Furthermore, studies evaluating anti-IL-17 agents in IBD patients were terminated early due to a disproportionate number of cases of worsening of Crohn's disease (CD) or lack of efficacy.6,7
Clinical studies of IL-23 and IL-12/23 inhibitors, which also target the IL-23/IL-17A axis for the treatment of psoriasis, have demonstrated efficacy and safety in patients with CD and/or ulcerative colitis (UC).8-10 In addition, IBD has not been identified as a safety concern in clinical studies of these biologic agents in psoriasis patients. A recent report focused specifically on
