Immunomodulation with methotrexate: underused and undervalued?

Therapeutic options for the treatment of inflammatory bowel disease (IBD) are multiple. There are excellent clinical trials showing in patients with IBD that immunomodulatory therapy is highly efficacious in the disease control in moderate active to severe forms. Most clinical experience was gained over the last years with the purine analogues azathioprine (AZA)/6-mercaptopurine (6-MP). These drugs are now considered as gold standard in the treatment of severe Crohn's disease (CD). However, for patients who fail to respond or who do not tolerate AZA/6-MP therapy, methotrexate is an interesting alternative drug. Two initial clinical trials validated the use of MTX in adult CD cohorts. There are now two retrospective analyses in pediatric cohorts available which nicely demonstrate the efficacy of MTX to maintain long-term remission in CD patients with active and severe disease progression. The remission rates are close to 50% in long-term follow-up, an efficacy comparable to purine analogues. Overall tolerance of MTX was good, with about 10% of adverse events in either study. Taken together, there are first data indicating that MTX might play a role comparable to AZA in the treatment of CD; however, to date it seems to be underused in the routine care of IBD patients.