Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders

Abstract

Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn's disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.

Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis

“…Unlike the recent narrative review of Hirten et al [3], that included no study about patients with active IBD treated with a combination of an Anti-TNF effective in IBD, vedolizumab or ustekinumab for a period of at least 3 months, we included 7 studies with a total of 18 patients. We excluded patients treated with etanercept, a fusion protein that blocks the TNF receptor without inducing lymphocyte apoptosis, since its ineffectiveness in the treatment of IBD; moreover it's the drug most frequently implicated in this immunologic toxicity [12].…”

“…A recent narrative review [3] included no studies about patients with active IBD treated with a combination of two among an Anti-TNF effective in IBD, vedolizumab or ustekinumab for a period of at least 3 months.…”

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease

“…Inability to achieve clinical remission or response deceases quality of life, and recurrent bowel resections can lead to complications such as short bowel syndrome with dependence on parenteral support, bile acid diarrhoea and nutritional deficiencies 1,7,8 . Thus, just as combination therapy with a biologic and immunomodulator is more effective than either alone, 6 the concomitant use of dual biologics that target different inflammatory pathways is a potential therapeutic approach in patients with severe and treatment refractory disease 9 . In all Crohn's disease patients, the simultaneous use of two biologic therapies can potentially lead to improved clinical and endoscopic outcomes.…”

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

“…A recent systematic review has summarized the limited available literature to date on combining biologics across a number of conditions. 152 They identified case reports and series in the dermatologic literature while a few controlled trials combining biologics have been conducted in rheumatoid arthritis, which failed to show improved efficacy, but these most commonly involved biologics not utilized in IBD such as etanercept, anakinra, abatacept, and rituximab. 153–155 In the IBD literature there have been a few case reports or series 156–159 suggestive of possible benefit and one published exploratory short-term controlled trial of combination biologic therapy, examining the safety and tolerability of concurrent natalizumab in 79 active CD patients despite infliximab therapy.…”