Evolution of Advanced Combination Treatment in Inflammatory Bowel Disease

Despite multiple new advanced therapeutic options for the treatment of inflammatory bowel disease (IBD), almost half of patients do not achieve clinical remission and the number requiring intestinal resection has not significantly changed in over 20 years. To address the therapeutic ceiling seen with single-agent biologics or small molecules, clinicians have attempted combination therapy, known as advanced combination treatment (ACT), to target multiple inflammatory pathways involved in IBD pathogenesis. ACT may be particularly helpful for patients with long-standing refractory disease and those with extraintestinal manifestations. Initial trials have supported the safety and efficacy of ACT, showing clinical and endoscopic remission rates of 59% and 34%, respectively, and response rates of 69% and 43%, respectively, and few new safety signals. However, increased adverse events are seen in patients combining ACT and immunomodulators or corticosteroids. Conclusions are limited by the lack of robust randomized controlled trial evaluation and aggregate analysis of outcomes. This article will review the available data on the use of specific ACT regimens in IBD.