P230 Methotrexate in the treatment of Crohn's disease: a Portuguese real-life single center experience
Peixoto A., Silva M., Morais R., Liberal R., Lopes S., Magro F., Macedo G.
Centro Hospitalar São João, Department of Gastroenterology, Porto, Portugal
Methotrexate (MTX) is frequently used as a second-line immuno-modulator in patients with Crohn's disease (CD) when purine analogs are not tolerated or lack efficacy. However, evidence on indications for its use, efficacy, adverse effects and patient outcomes is still limited. Our objective was to evaluate the experience with the use of MTX in CD in a high-volume Portuguese tertiary center.
The records of all patients treated with MTX were evaluated with regard to the dose, duration, response, and tolerance to MTX. Remission was defined as improvement in symptoms with no corticosteroid requirement for 3 months or ability to wean off steroids.
Sixty-two patients were included, 35 female (56.5%), with a mean age of 37.5 (± 11.3) years. According to the Montreal classification, the distribution of the disease was as follows: age - A1 12.9%, A2 46.8%, A3 38.7%; location - L1 27.4%, L2 12.9%, L3 51.6%, L1+4 1.6%; behavior - B1 33.9%, B2 25.8%, B3 40.4%. Twenty-one patients had perianal disease (33.9%) and half had previous surgery. MTX was the first-line immunosuppressant in 9 patients (14.5%). Indications for initiating MTX included: adjuvant to anti-TNF agent (43.5%), intolerance to azathioprine (27.4%), corticodependence (19.4%) and corticoresistance (9.7%). Almost half of the patients were on steroids at the onset of MTX (n=28, 47.5%). Eighteen patients achieved clinical remission under MTX (29%), 22 clinical response (35.5%) and 22 were nonresponders (35.5%). Absence of response was associated with a lower cumulative dose (784 vs. 1365 mg, p=0.004), shorter duration of treatment (66 vs. 89 weeks, p=0.003), diagnosis at an earlier age (21 vs. 27 years, p=0.028), and colonic involvement (48% vs. 0%, p=0.006). During treatment with MTX 35.5% developed flare(s), 37.1% needed steroids, 9.7% started anti-TNF agent, and 12.9% had surgery. Forty-nine patients discontinued MTX after a mean period of 88 (±86) weeks. Reasons for suspension included hepatitis (34%), absence/loss of response (31.2%), intolerance (17%), patient decision (14.9%) and pregnancy (2.1%). In total, 21 patients had adverse effects (36.8%) and 4 (6.9%) had opportunistic infections, all of them under anti-TNF. After MTX discontinuation, 43.6% of the patients had further flare(s), 20.4% started anti-TNF agent, and 12.7% underwent surgery.
Despite the moderate efficacy demonstrated in the management of Crohn's disease, mainly as an adjuvant to anti-TNF agents, the use of MTX is limited by the development of adverse effects by more than 30%. Longer treatment, especially in patients with localized ileal disease, is associated with higher response rates.