title: Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease.
abstract: This systematic review investigated the efficacy and the effectiveness of biologic drugs in extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD).
  
  
  
  Literature search was conducted in PubMed, Embase, and Cochrane until October 2015. Main inclusion criteria were adults with IBD, use of a biologic drug, evolution of EIMs, interventional study, or non-interventional study.
  
  
  
  Nine interventional studies (2 randomized controlled trials [N = 797], 7 open label trials [N = 1143], and 13 non-interventional studies [N = 914]) were included. Tumor necrosis factor (TNF) antagonists achieved complete response for pyoderma gangrenosum in 21%-25% of patients in interventional studies and in 92%-100% patients in non-interventional studies, with similar results for other cutaneous manifestations such as erythema nodosum or stomatitis. Adalimumab significantly reduced the prevalence of anemia vs placebo after 56 weeks in 1 randomized controlled trial. In 2 non-interventional studies, anti-TNF therapy improved anemia in the short-term (67%) and in the long-term (34%). Complete response after anti-TNF treatment was reported in interventional studies, including arthralgia (reduction in prevalence from 47.1% to 26.8% in the mid-term in 1 open label trial) and arthritis (reduction in prevalence from 8.7% to 2.1% and from 58% to 12.5% in 2 open label trials). Anti-TNFs were beneficial for a majority of patients with ocular manifestations. Infliximab was associated with improved outcomes in bone formation and bone mineral density.
  
  
  
  Anti-TNFs appear to be effective alternatives for certain EIMs associated with IBD including musculoskeletal, cutaneous, and ocular manifestations, and some beneficial effect may be obtained in metabolic bone disease and on hematologic or vascular EIMs.
authors.affiliation: Gastroenterology Department, Lorraine University, Vandoeuvre, France. Electronic address: peyrinbiroulet@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: IMS Health, Real-World Evidence Solutions, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Ulloa
authors.affiliation: IMS Health, Real-World Evidence Solutions, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Álvarez
authors.affiliation: IMS Health, Real-World Evidence Solutions, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Lara
authors.affiliation: Center for Observational and Real-World Evidence (CORE), Merck and Co, Inc, Kenilworth, New Jersey.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Black
authors.affiliation: Center for Observational and Real-World Evidence (CORE), Merck and Co, Inc, Kenilworth, New Jersey.
authors.forename: Sumesh
authors.initials: S
authors.lastname: Kachroo
mesh_terms: D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D001688:Biological Products; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
keywords: Extraintestinal Manifestations; Inflammatory Bowel Disease; Systematic Review