Sustained clinical benefit and tolerability of methotrexate monotherapy after thiopurine therapy in patients with Crohn's disease.

Background & Aims: Methotrexate is an immunosuppressant that is used to treat patients with Crohn's disease (CD). However, there are few data on the long-term effects of methotrexate maintenance therapy for these patients. We assessed the sustained clinical benefits and tolerability of methotrexate monotherapy after thiopurine therapy in patients with CD.

Methods: We analyzed data from 3 hospitals on 174 consecutive patients with CD (age, 35 ± 12 y) who received methotrexate monotherapy after thiopurine therapy (23% also did not respond to anti-tumor necrosis factor therapy) from 2000 to 2010. We assessed patient characteristics and the tolerability and sustained clinical benefits of the treatment. Sustained clinical benefit was defined as ongoing use of methotrexate or intentional discontinuation of successful therapy before the end-of-study point.

Results: The number of patients with sustained clinical benefits from methotrexate monotherapy were 98 (86%), 50 (63%), 27 (47%), and 3 (20%), at 6, 12, 24, and 60 months, respectively. Forty-five patients (26%) discontinued methotrexate because of intolerance, particularly within 6 months after therapy began. Adverse responses generally were mild; only 1 patient required admission to the hospital for infection with cytomegalovirus, and no drug-related deaths were reported. Intolerance of the preceding thiopurine therapy was associated with adverse events during methotrexate therapy.

Conclusions: In a large cohort study of patients who received methotrexate monotherapy after thiopurine therapy for CD, 47% continued to receive the therapy or intentionally discontinued successful therapy within 2 years, and 20% did so within 5 years. Long-term use of methotrexate was well tolerated and relatively safe.