Advanced combination therapy in IBD

Abstract

Conventional combination therapy in inflammatory bowel disease (IBD), which consists of an immunosuppressant agent and an anti-TNF agent, is a well-integrated strategy in clinical practice. The landmark SONIC and UC SUCCESS trials demonstrated that combining a thiopurine and infliximab was more effective than monotherapy and was associated with higher corticosteroid-free remission and mucosal healing rates. The primary advantage of this traditional combination therapy derives from the immunomodulator’s effect on the pharmacokinetics of anti-TNFs, with a lower rate of anti-drug antibodies detected in subjects administered combination therapy. Despite the growing therapeutic armamentarium and clinical study development pipeline for IBD, clinical remission rates at one year continue to range from 30% to 50%, indicating that a therapeutic ceiling may have been reached with the use of single agents. In addition, agents that have proven effective for luminal disease may not be helpful for extraintestinal manifestations (EIMs) or for concurrent immune-mediated diseases (IMIDs). In light of this, the concept of advanced combination treatment (ACT), which entails the simultaneous administration of at least two biologic agents, or a biologic and a small-molecule drug, is emerging as a therapeutic approach for patients with refractory IBD, as well as for those with IBD and a concurrent IMID, or IBD with EIMs.