title: Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials.
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.
  
  
  CONCLUSIONS
  Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence.
  
  
  CONCLUSIONS
  From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).
authors.affiliation: Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.affiliation: Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: Craig
authors.initials: C
authors.lastname: Leonardi
authors.affiliation: Division of Clinical Dermatology and Cutaneous Science, Dallhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Langley
authors.affiliation: Dermatology Centre, Salford Royal Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Warren
authors.affiliation: 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.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bachelez
authors.affiliation: Department of Dermatology Hospital das Clínicas University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Romiti
authors.affiliation: Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Nayan
authors.initials: N
authors.lastname: Acharya
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Solotkin
authors.affiliation: Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana. Electronic address: hardin_dana_sue@lilly.com.
authors.forename: Dana S
authors.initials: DS
authors.lastname: Hardin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000453:epidemiology*; D003424:Crohn Disease / Q000139:chemically induced / Q000453:epidemiology*; D016208:Databases, Factual; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D060828:Induction Chemotherapy / Q000009:adverse effects; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; C549079:ixekizumab
keywords: Crohn's disease; biologic therapy; inflammatory bowel disease; interleukin-17 antagonists; ixekizumab; psoriasis; ulcerative colitis