Indication of conventional combotherapy in IBD in 2024

Indication of conventional anti-TNF and immunosuppressant (thiopurine, methotrexate) combination therapy is questionable due to the risk of immunogenicity and a poorer safety profile than the new biotherapies, for which the rationale for use in combination has not been demonstrated. Nonetheless, it continues to play a major role in IBD in patients naive of biologics, with less evidence for adalimumab and with methotrexate, which remains however a valid therapeutic option in elderly patients and those with severe comorbidities. Its use in severe acute colitis in UC is well documented, and its use in fistulizing anal lesions in Crohn’s disease is recommended in current practice. Combination therapy is also an option in moderate-to-severe UC and Crohn’s disease. When switching anti-TNF agents, the combination with an immunosuppressant is mandatory, as it improves treatment efficacy, mainly by reducing the risk of immunogenicity. In case of clinico-biological remission, a discontinuation of the immunosuppressant after 6 to 12 months should be discussed in order to limit the risk of toxicity. As experience with combiotherapies (combination of biologics) is limited and the safety profile uncertain, conventional combotherapy remains a major therapeutic option in IBD in 2024.