Advanced combination therapy: is it the best way to break the therapeutic ceiling?

Current therapeutic strategies for inflammatory bowel disease (IBD) have reached a plateau in the rates of response and/or remission achieved with a single therapeutic agent. Consequently, the advanced combination therapy (ACT) strategy has emerged as a novel treatment concept for IBD. ACT involves the use of two different targeted therapies, whether biologic or small molecules, with the primary goal of overcoming the therapeutic plateau. Real-world evidence is accumulating among patients undergoing ACT, especially those dealing with concurrent IBD and extraintestinal manifestations or grappling with medically refractory IBD. The recently conducted VEGA study, a randomized clinical trial, has provided crucial insights by demonstrating that the short-term combination of dual biological agents can lead to superior disease control compared to single agents in patients diagnosed with ulcerative colitis (UC). This suggests that ACT holds promise as a therapeutic option to enhance disease control effectively. However, there is still limited evidence of ACT in UC patients who have proven refractory to biologic therapy and patients with Crohn's disease. This review aims to discuss whether ACT represents the optimal approach for overcoming the therapeutic ceiling in IBD.