Introduction Methotrexate (MTX) is used as an immunosuppressive treatment in inflammatory bowel disease (IBD). The aim of the study was to evaluate the long-term tolerability of MTX in adults with IBD from a large, single, tertiary referral centre.
Methods IBD patients who had received MTX at a single centre between 2000 – 2011 were identified from the IBD service database and clinical records reviewed.
Results 137 patients received MTX (Crohn’s Disease 105 (77%); ulcerative colitis (UC) 32 (23%)); mean age 44 (range 18–77). The median duration of MTX treatment was 13 months (range 1–127) with an initial dose of 25mg/week (range 10–25 mg) in 127/137 (93%) with 94% commencing MTX intramuscularly. The proportion who continued MTX for ≥ 3, 5, 10 years were 24% (33/137), 10% (14/137) and 1.5% (2/137) respectively.
89/137 (65%) discontinued MTX during the 11 year follow-up. The cessation rate due to lack of effectiveness was 17/137 (12%) by the end of the 2nd year of MTX, after which there were no further discontinuations for this reason. 77/137 (57%) reported ≥ 1 side-effect (SE) attributed to MTX, which was the commonest reason for discontinuing MTX (61/89; 69%). SEs leading to MTX cessation were most frequent during induction (defined as 0–3months): 22/61 (36%); followed by 3–12 months following initiation of MTX: 16/61 (26%). Specific SEs resulting in cessation during the 1st year of MTX were due to ≥ 1 of the following; 15 (40%) gastrointestinal (GI), 12 (32%) neurological (NS), 5 (13%) nonspecific malaise, 5 (13%) abnormal hepatic aminotransferase levels (2-fold increase up to or over the upper limit of normal), 2 (5%) hair loss, 5 other (1 each of sore throat, rash, infection, low platelets, injection site reaction). The incidence of discontinuation due to SEs in successive MTX years fell from commencement of MTX: 10/61 (16%) in the 2nd year, 5/61 (8%) in the 3rd year, 3/61 (5%) in the 4th year and 5 (8%) in total between the 5th-10th years. The most frequent SEs attributed to late discontinuation ( > 1year) were GI and NS.
Over 11 years there were 12/137 (9%) reported cases of presumed MTX induced abnormal hepatic aminotransferase levels, of which 8 (67%) resulted in MTX cessation with biochemical resolution. Hepatotoxicity occurred during induction in 7/12 cases (58%) and was stopped in 5 of these (71%). In 5 patients with late abnormal hepatic aminotransferase levels, the median time to detection was 36 months (range 10–100months). MTX was discontinued in 3 of these.
Conclusion In the largest single-centre experience to date, MTX in IBD is limited by high withdrawal rates with a 28% discontinuation rate due to SEs within the 1st year. Late hepatoxicity highlights the need for long term monitoring in maintenance therapy.
Disclosure of Interest None Declared
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