Combination therapy in inflammatory bowel disease – from traditional immunosuppressors towards the new paradigm of dual targeted therapy

Background: Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD). Aim: To summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies. Methods: A literature search on PubMed and Medline databases was performed to identify relevant articles. Results: Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn's Disease and Ulcerative colitis. Data on other combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far. Conclusions: Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.