Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies.