Long-term methotrexate for Crohn's disease: safety and efficacy in clinical practice

Goals: To assess the efficacy and safety profile of methotrexate (MTX) for the treatment of Crohn's disease (CD) in clinical practice. Background: MTX is widely used for some chronic immunologic diseases. Although some randomized controlled trials suggest its efficacy in CD, this drug remains a second-line, underused, immunomodulator. Study: Medical records of all patients treated with MTX for CD in our center (n = 44) were reviewed. Clinical and epidemiologic parameters, including risk factors for hepatotoxicity, were registered. Results: MTX was prescribed mainly for steroid-dependency (n = 22) and as concomitant treatment to infliximab (n = 18). Mean duration of treatment was 22.9 ± 19 months, with a mean cumulative dose of MTX of 1169 ± 784 mg. Thirty-nine percent of patients developed drug-related side effects, hepatotoxicity being the most frequent [13 patients (30%)]. However, only 5 patients (11%) had to discontinue MTX. In steroid-dependent CD patients, disease remission and complete steroid withdrawal was achieved in 77% of cases. Seven patients lost their initial response to MTX during follow-up, leading to a cumulative probability of remission of 39% after 3 years of treatment. Conclusions: MTX is well tolerated in most CD patients. Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal, there is a trend to a loss of efficacy with time. Larger, long-term studies are necessary to establish the role of MTX in the management of CD.