Background: The majority of children with ulcerative colitis (UC) are likely to need some form of immunomodulators to maintain remission and to avoid long-term corticosteroid usage. Although thiopurine agents are commonly used, some children are unresponsive or intolerant to these drugs. Few data are available to assess the efficacy of methotrexate (MTX) in the treatment of UC. The present report describes our experience of using MTX in UC children.
Methods: Twenty-four patients (50% male, 50% female; age range 8.3–19.8 years; median 13.9 years) with UC treated with MTX were identified from the departmental database. Case records were reviewed for site of disease, age at diagnosis, duration of disease before the introduction of MTX, indication to MTX use, and side effects of therapy. Pediatric Ulcerative Colitis Activity Index and corticosteroid (CS) use were evaluated baseline at 3, 6, and 12 months.
Results: Ulcerative colitis was diagnosed at a mean age of 10 ± 4.3 years. Pancolitis was diagnosed in 18 of 24 patients (75%), left-sided colitis in 4 patients (16%), and proctitis in 2 patients (8%). MTX was introduced 23.4 ± 12.3 months after diagnosis. Indications to MTX therapy were a nonresponse to or relapse under azathioprine (n = 15), azathioprine intolerance/toxicity (n = 7), or spondyloarthropathy (n = 2). The mean dose of MTX for a patient was 13.7 ± 3.6 mg · m−2 · week−1. Clinical remission was achieved in 18 of 24 patients (75%): 55% of patients at 3 months, 13% of patients at 6 months, and 9% of patients at 12 months. Among these, 4 patients (22%) relapsed after 10 ± 2 months. Mean Pediatric Ulcerative Colitis Activity Index was 49.5 ± 23.3 baseline, 32.9 ± 21.9 at 3 months (P < 0.05), 29.5 ± 22.8 at 6 months, and 29.4 ± 25.9 at 12 months (not statistically significant).
At the beginning of MTX treatment 10 of 24 patients (41%) were treated by CS, of whom 8 patients (80%) discontinued CS by 6 months. At 12 months 25% of the patients needed CS for relapsing of disease. The dose of MTX (more than or equal to 15 mg/week) was associated with the induction of remission (P < 0.02). Adverse reactions were observed in 8 patients (33%) (liver enzyme elevation n = 1, fever n = 3, nausea n = 3), requiring discontinuation of MTX in 2 patients (8%) (1 because of intractable nausea and 1 because of recurrent fever).
Conclusions: Our data suggest that MTX therapy is effective in maintaining remission and reducing CS exposure in pediatric UC. Methotrexate could be considered in those patients who escaped or did not tolerate thiopurines. Nevertheless, large, controlled trials are warranted to better define the role of MTX in pediatric UC.
The authors report no conflicts of interest.