Original article
Systematic reviews and meta-analyses
Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease

https://doi.org/10.1016/j.cgh.2016.06.025Get rights and content

Background & Aims

This systematic review investigated the efficacy and the effectiveness of biologic drugs in extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD).

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Methods

The scope of the systematic review was defined in a protocol that guided the development of search strategy, study selection, data extraction, and reporting.

Efficacy (Interventional Studies)

A flow diagram depicting the findings of the searches and the selection process is provided in Supplementary Figure 1. A total of 1403 potentially relevant citations were identified through the literature search, and 4 additional citations were identified through manual searches or by reviewing the citations of studies selected. Removal of duplicates followed by review of titles and abstracts and review of full texts yielded 9 relevant studies that fulfilled the eligibility criteria and were

Discussion

Despite the increased interest in the potential use of biologic drugs for the management of EIMs in IBD patients, our systematic review indicates that the number of studies assessing their efficacy or effectiveness for this indication remains limited, especially in UC. However, evidence available from interventional and non-interventional studies suggests that the clinical benefit from infliximab or adalimumab may not be restricted to the local intestinal effect but expand to ameliorate or cure

References (49)

  • R.J. Robinson et al.

    Osteoporosis and determinants of bone density in patients with Crohn's disease

    Dig Dis Sci

    (1998)
  • I.E. Koutroubakis et al.

    Low bone mineral density in Greek patients with inflammatory bowel disease: prevalence and risk factors

    Ann Gastroenterol

    (2011)
  • P. Frei et al.

    Analysis of risk factors for low bone mineral density in inflammatory bowel disease

    Digestion

    (2006)
  • E.J. Schoon et al.

    Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch population-based cohort

    Scand J Gastroenterol Suppl

    (2000)
  • Z. Pellicer et al.

    Management of cutaneous disorders related to inflammatory bowel disease

    Ann Gastroenterol

    (2012)
  • X.Q. Ji et al.

    Pulmonary manifestations of inflammatory bowel disease

    World J Gastroenterol

    (2014)
  • R. Peluso et al.

    Management of arthropathy in inflammatory bowel diseases

    Ther Adv Chronic Dis

    (2015)
  • M. Harbord et al.

    The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease

    J Crohns Colitis

    (2016)
  • G. Andrisani et al.

    Anti-TNF alpha therapy in the management of extraintestinal manifestation of inflammatory bowel disease

    Eur Rev Med Pharmacol Sci

    (2012)
  • A. Barrie et al.

    Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel disease

    Inflamm Bowel Dis

    (2007)
  • M. Zippi et al.

    Biological therapy for dermatological manifestations of inflammatory bowel disease

    World J Clin Cases

    (2013)
  • S.R. Vavricka et al.

    Biologics for extraintestinal manifestations of IBD

    Curr Drug Targets

    (2014)
  • A. Liberati et al.

    The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

    BMJ

    (2009)

  • Undertaking systematic reviews of research on effectiveness. CRD Report 4

    (2001)

    • Cited by (96)

    View all citing articles on Scopus

    Conflicts of interest Laurent Peyrin-Biroulet has received lecture fees from Merck, AbbVie, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi, and HAC-Pharma and consulting fees from Merck, AbbVie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-Pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, Amgen, Sandoz, and Forward Pharma GmbH. Gert Van Assche has received research support from the University of Leuven, AbbVie, and MSD, speaker's fees from AbbVie, Ferring, MSD, and Janssen, and consulting fees from the University of Leuven, AbbVie, MSD, Ferring, UCB, and Takeda. David Gómez-Ulloa is a consultant for Merck. Laura García-Álvarez is a consultant for Merck. Núria Lara is consultant for Merck. Chris M. Black is a Merck stockholder and Merck employee. Sumesh Kachroo is a Merck stockholder and Merck employee.

    Funding This manuscript was conducted by IMS Health with financial support from Merck & Co.

    View full text
    © 2017 by the AGA Institute