P585 Systematic literature review of clinical trials that assess the efficacy of biologic drugs in the treatment of extraintestinal manifestations in inflammatory bowel disease
G. Van Assche1, L. Peyrin-Biroulet2, D. Gomez-Ulloa3, L. Garcia-Alvarez3, N. Lara3, C. Black4, S. Kachroo*4
1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium, 2Lorraine University, Gastroenterology Department, Vandoeuvre, France, 3IMS Health, Real-World Evidence Solutions, Barcelona, Spain, 4Merck & Co, Inc, Centre for Observational and Real-World Evidence (CORE), Rahway, New Jersey, United States
Extraintestinal manifestations (EIMs) are common in patients with inflammatory bowel disease (IBD). New biologic drugs approved for IBD in the last few years have been suggested to improve the outcomes of EIMs. The objective of this systematic literature review (SLR) is to assess previously published clinical trials (CT) investigating the efficacy of biologic drugs in the treatment of EIMs in IBD.
A SLR was conducted in PubMed, Embase, and Cochrane in October 2015. Main inclusion criteria was comprised of adults with IBD, use of a biologic drug (infliximab [IFX], adalimumab [ADA], certolizumab pegol [CZP], golimumab [GOL], vedolizumab [VED], natalizumab [NAT]), evolution of EIMs (ie, musculoskeletal, metabolic bone disease [MBD], cutaneous, ocular, hepatobiliary, vascular, or haematologic]), CTs, and English language. Key exclusion criterion was observational studies and conference abstracts. Data were abstracted from indexed publications.
Included were 9 CTs (1 940 IBD patients analysed); 2 were randomised controlled trials (RCTs), assessing IFX in pyoderma gangrenosum (PG) in IBD, and ADA in anaemia in Crohn’s disease (CD); 7 were open-label (OL) trials evaluating the efficacy of IFX (4 studies) and ADA (3 studies) in multiple EIMs (musculoskeletal, cutaneous, ocular, vascular, and haematologic) in CD patients. In one RCT, the use of IFX for the treatment of PG was associated with a significant increase of responders in the short term (2 weeks) vs placebo (46% vs 6%, p = 0.025). In the second RCT, patients treated with ADA weekly and ADA every other week showed significantly reduced prevalence of anaemia vs those on placebo after 56 weeks (20.7%, 25.2%, and 31.9%, respectively, p < 0.05 for both comparisons vs placebo). Short- (range follow-up 2–12 weeks) and long-term (follow-up 18 months) OL trials assessing the efficacy of IFX treatment reported clinical improvement or resolution of musculoskeletal manifestations, including arthralgia and arthritis. Short-term OL trials also reported a positive response to IFX in cutaneous manifestations, including PG and aphthous ulcers and in ocular manifestations. ADA studies showed mid-term clinical improvement from baseline (follow-up 6 months) in several EIMs, including musculoskeletal, cutaneous, ocular, and MBD. Studies assessing the efficacy of CZP, GOL, VED, or NAT were not identified.
Our SLR indicates that very few RCTs assessing the efficacy of biologic drugs in EIMs suffered by IBD patients are available. IFX and ADA have shown efficacy in the treatment of certain EIMs associated with IBD (musculoskeletal, MBD, cutaneous, and ocular), particularly in CD. Data on the efficacy of biologic drugs in ulcerative colitis patients are scarce.