P748 Clinical outcomes and prognostic factors of methotrexate therapy in combination with anti-TNF agents in inflammatory bowel disease

Abstract

Combination therapy with an immunomodulator and anti-tumour necrosis factor (TNF) is one of the crucial therapeutic strategies for inflammatory bowel disease (IBD) management. Methotrexate (MTX) is a second-line immunomodulator and has received much attention in recent years due to several advantages over thiopurine. We aimed to investigate clinical outcomes and prognostic factors of MTX therapy when combined with anti-TNF in IBD patients. We retrospectively reviewed 70 IBD patients (Crohn’s disease [n = 57], Ulcerative colitis [n = 13]) (age, 18–63 years) treated with MTX in combination with anti-TNF agents for induction or maintenance therapy at Severance and Gangnam Severance Hospital, Seoul, Korea. 22 (31.4%) were initially commenced on oral and 48 (68.6%) started subcutaneous route. Initial MTX dosage was 7.5–25.0 mg/week. Drug data for MTX therapy and outcomes data for clinical efficacy were analysed. Moreover, sustained clinical benefit of MTX therapy which was defined as ongoing use of MTX or intentional discontinuation of successful therapy before last follow-up was also evaluated. Recruitment algorithm. A total of 49 patients were selected for the analysis of induction therapy, and steroid free clinical remission was achieved in 22 (44.9%) of the 49 patients at 3 months, 13 (50.0%) of the 26 patients at 12 months, and 4 (44.4%) of the 9 patients at 24 months. Co-therapy with second line anti-TNF agent was associated with a failure of clinical remission at 3 months (odds ratio [OR]: 0.084, 95% confidence interval [CI]: 0.009–0.838). Meanwhile, 60 patients were selected for the analysis of maintenance therapy, and 17 (28.3%) patients experienced relapse during follow-up period of 3–26 months. Anaemia (Haemoglobin < 11 mg/l) at maintenance initiation was independent predictor of relapse (hazard ratio [HR]: 3.847, 95% CI: 1.153–12.829). Factors related with failure of sustained clinical benefit of MTX in combination therapy were obesity (≥23 kg/m2) (HR: 4.117, 95% CI: 1.380–12.296), concomitant adalimumab (vs. infliximab) therapy (HR: 3.872, 95% CI: 1.419–10.571), and female sex (HR: 3.271, 95% CI: 1.119–9.561). Adverse event related with MTX occurred in 24 (34.3%) patients, and 3 (4.3%) patients discontinued MTX due to adverse event. MTX therapy in combination with anti-TNF was relatively well tolerated. The type of combined anti-TNF agents and baseline patient characteristics rather than the MTX dosage and administration route were crucial factors in determining clinical outcome.