In patients previously treated with thiopurine, risk for adverse reaction was low with methotrexate monotherapy, but so was the rate of sustained response.

In treating patients with Crohn disease, clinicians typically use anti–tumor necrosis factor (anti-TNF) agents and the immunomodulatory agents azathioprine and 6-mercaptopurine before methotrexate. Gastroenterologists tend to be concerned about the long-term risks of methotrexate, including liver fibrosis, although recent studies suggest that the risk for cirrhosis is considerably lower than previously thought. Now, investigators have retrospectively assessed the long-term response and safety of methotrexate for Crohn disease.

The study cohort of 174 patients (mean age, 35 years; median disease duration, 4 years) received intramuscular methotrexate monotherapy following thiopurine therapy, with 23% also having received but not responded to anti-TNF therapy. Patients received 25 mg of methotrexate weekly, eventually tapering to 15 mg. The most common indication was intolerance of a thiopurine (55%), followed by clinical failure of thiopurines (24%), failure of anti-TNF monotherapy (9%), and failure of combination anti-TNF agents and thiopurines (12%). A sustained clinical benefit was defined as ongoing use of methotrexate or intentional discontinuation of successful therapy (e.g., in anticipation of pregnancy) prior to the end of study.

Patients intolerant of thiopurine were more often intolerant of methotrexate than were patients in whom methotrexate was initiated for thiopurine failure (22 vs. 6). The rate of sustained clinical benefit of monotherapy methotrexate was 86% at 6 months; 63% at 12 months; 47% at 24 months; and 20% at 60 months. The most common reasons for discontinuation were adverse reaction (56%; most frequently GI complaints and general malaise, including fatigue, fever, dizziness, and headache); loss of response (38%); and primary nonresponse (5%). No liver biopsies were taken, and only 6% of discontinuations were for asymptomatic increases in liver enzymes.

Comment: This study indicates that when used in patients with thiopurine failure in Crohn disease, methotrexate has a low risk for adverse reactions, but also a relatively low long-term sustained response rate.

Source: Journal Watch Gastroenterology