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OC-018 Limited long Term Tolerance of Methotrexate For Inflammatory Bowel Disease: 11 Years Experience from a Single Centre
  1. A J Brooks1,
  2. E M Wood1,
  3. K Robinson1,
  4. A Wright1,
  5. M E McAlindon1,
  6. A J Lobo1
  1. 1Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK

Abstract

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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