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P239. Methotrexate as a third-line therapy after thiopurine and anti‑TNF failure in Crohn's disease


W. Diaz-Saa1, D. Carpio-Lopez1, E. Fernandez-Salgado1, M.V. Alvarez-Sanchez1, S. Vazquez-Rodriguez1, V. Gonzalez-Carrera1, A. Ledo-Rodriguez1, R. Baltar-Arias1, E. Castro-Ortiz1, E. Vazquez-Astray1, J. Turnes-Vazquez1

1Complexo Hospitalario de Pontevedra, Spain



Background: Methotrexate (MTX) has demonstrated efficacy for treating Crohn's disease (CD). In most of studies it's used after thiopurine failure. However, it's not yet been described its scope after anti‑TNF withdrawal.

Methods: Our aim was to assess the efficacy of MTX for the treatment of CD in clinical practice as a third-line therapy.

We conducted a retrospective study in a second-level hospital, registering data from outpatient clinic records within 2004 and 2010. After revising our database, we found 41 patients treated anytime with MTX 25 mg/subcutaneous/weekly. 21 out of these patients had received previously thiopurines and anti‑TNF (20 IFX, 1 ADA) which were inefficient/toxic.

We recorded patient's clinical and demographic characteristics, history of past treatments, causes of thiopurine discontinuation, type of anti‑TNF and corticosteroid (CE) dependence.

We assessed patient's clinical outcomes retrospectively by determining the Harvey–Bradshaw Index (HBI) before MTX and at 4th, 6th and 12th month after starting it. We considered clinical remission as a HBI≤4 points and clinical response as a decrease of 2 points. Patients who didn't have that decrease or discontinued MTX were considered as non responders.

Side effects, flares and their therapies, CE tapering and reasons of MTX discontinuation were also registered.

Results: 21 patients were included, 12 women; median age 38 years, range 29–48. 52.38% had colonic extension, 14.29% upper gastrointestinal tract involvement and 85.71% perianal disease. 85.71% presented extraintestinal affectation. A 47.62% of them had gone through resective surgery once. Most of them were CE-dependant (66.67%). Thiopurines were withdrawn due to inefficiency in 90.48%. Median HBI before treatment was 7 points, range 2–15.

Clinical outcomes are shown in the table.

TimeRemission (%)Response (%)Clinical benefit (%)Non response (%)
4 months28.5714.2942.8657.14
6 months14.2923.8138.161.90
12 months22.2211.1133.3366.67

Conclusions: MTX seems to be moderately effective as a third-line therapy after thiopurine and anti‑TNF failure in this particularly difficult to treat cohort.

MTX is well tolerated, with a low number of side effects leading to withdrawal.

1. Patel (2009), Methotrexate for maintenance of remission in Crohn's disease, Cochrane Database Syst Rev.

2. Haussmann (2010), Methotrexate for maintenance of remission in chronic active Crohn's disease: long-term single-center experience and meta-analysis of observational studies, Inflamm Bowel Dis.

3. Best (2006), Predicting the Crohn's disease activity index from the Harvey–Bradshaw Index, Inflamm Bowel Dis.