When to Start Immunomodulators in Inflammatory Bowel Disease?

Abstract

Background: Immunomodulators (IMMs), including thiopurines (TPs) and methotrexate (MTX), are commonly used in the treatment of inflammatory bowel disease (IBD). Key Messages: In ulcerative colitis (UC), TPs have modest steroid-sparing effects and established efficacy in maintenance of remission. The role of MTX in UC is unclear but current evidence suggests no benefit over placebo. In Crohn's disease (CD), MTX is not effective for induction but has a modest steroid-sparing effect and is superior to placebo in maintenance of remission in responders. The addition of MTX to infliximab reduces immunogenicity and boosts infliximab levels but does not improve outcomes in active CD. TPs are not effective for induction of remission in CD but have proven steroid-sparing effects and modest efficacy in maintenance of remission and prevention of postoperative recurrence. Although effective in pediatric CD, recent evidence has questioned the benefit of early TPs in newly diagnosed adult CD. The addition of TPs to infliximab reduces immunogenicity and inflammatory markers, leads to higher infliximab levels and improves outcomes in patients with early disease. However, the benefit of continued TP therapy in this setting is unclear and should be weighed against possible side effects including an increased risk of opportunistic infections, lymphoma and non-melanoma skin cancer. Conclusions: IMMs are an important therapeutic option in IBD particularly in non-severe steroid-dependent disease and for maintenance of remission. Combination with anti-TNF agents is an important emerging option as part of a treat-to-target strategy but further research regarding patient selection, long-term use and de-escalation options is needed.