Combination therapy for inflammatory bowel disease

Abstract

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy (CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn’s disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment naïve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC’s conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

Keywords: Crohn’s disease, Adalimumab, Vedolizumab, Ulcerative colitis, Infliximab, Inflammatory bowel disease, Methotrexate, Azathioprine

Core tip: The benefits of combination therapy (CT) with infliximab and azathioprine likely outweigh its risks in treatment naïve patients with moderate to severe Crohn’s disease and ulcerative colitis. A similar benefit in patients already failing biologics or immunomodulators is not as well defined. There is a lack of strong prospective evidence demonstrating a benefit for CT with adalimumab and an immunomodulator. While expert guidelines emphasize the use of CT, its use should be preceded by a careful weighing of the risks and benefits by the physician and patient, especially in scenarios where the strongest evidence for CT may not directly apply.