Kristian Reich1, Craig Leonardi2, Richard G Langley3, Richard B Warren4, Hervé Bachelez5, Ricardo Romiti6, Mamitaro Ohtsuki7, Wen Xu8, Nayan Acharya8, Kathleen Solotkin8, Jean-Frederic Colombel9, Dana S Hardin10. 1. Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany. 2. Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, Missouri. 3. Division of Clinical Dermatology and Cutaneous Science, Dallhousie University, Halifax, Nova Scotia, Canada. 4. Dermatology Centre, Salford Royal Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. 5. Sorbonne Paris Cité Université Paris Diderot, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherché 1163, Imagine Institute, Necker Hospital, Paris, France. 6. Department of Dermatology Hospital das Clínicas University of São Paulo, São Paulo, Brazil. 7. Jichi Medical University, Shimotsuke, Japan. 8. Eli Lilly and Company, Indianapolis, Indiana. 9. Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. 10. Eli Lilly and Company, Indianapolis, Indiana. Electronic address: hardin_dana_sue@lilly.com.
Abstract
BACKGROUND: Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown. OBJECTIVE: We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. METHODS: Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry). RESULTS: In all, 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date. LIMITATIONS: Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence. CONCLUSION: From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).
BACKGROUND:Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown. OBJECTIVE: We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. METHODS: Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry). RESULTS: In all, 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date. LIMITATIONS: Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence. CONCLUSION: From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).
Authors: Michael M Ward; Atul Deodhar; Lianne S Gensler; Maureen Dubreuil; David Yu; Muhammad Asim Khan; Nigil Haroon; David Borenstein; Runsheng Wang; Ann Biehl; Meika A Fang; Grant Louie; Vikas Majithia; Bernard Ng; Rosemary Bigham; Michael Pianin; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Jeff Oristaglio; Amy Turner; Walter P Maksymowych; Liron Caplan Journal: Arthritis Care Res (Hoboken) Date: 2019-08-21 Impact factor: 4.794
Authors: Michael M Ward; Atul Deodhar; Lianne S Gensler; Maureen Dubreuil; David Yu; Muhammad Asim Khan; Nigil Haroon; David Borenstein; Runsheng Wang; Ann Biehl; Meika A Fang; Grant Louie; Vikas Majithia; Bernard Ng; Rosemary Bigham; Michael Pianin; Amit Aakash Shah; Nancy Sullivan; Marat Turgunbaev; Jeff Oristaglio; Amy Turner; Walter P Maksymowych; Liron Caplan Journal: Arthritis Rheumatol Date: 2019-08-22 Impact factor: 15.483