Optimal Doses of Methotrexate Combined with Anti-TNF Therapy to Maintain Clinical Remission in Inflammatory Bowel Disease

Background and aims: Methotrexate (MTX) is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease [IBD]; however, the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis factor alpha (anti-TNF) therapy among IBD patients. Methods: Retrospective chart review was performed of 88 IBD patients at our center between 2010 and 2013. Low-dose MTX was defined as <= 12.5 mg/week and high-dose MTX as 15-25 mg/week. Patients who met the criteria for clinical remission [Harvey-Bradshaw Index <= 4, Simple Clinical Colitis Activity Index <= 2] at baseline were followed for up to 42 months. Chart review occurred in 6-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease [endoscopic inflammation, steroid use, therapy escalation/addition, or surgery] and adverse events. Regression analysis and Kaplan-Meier survival analysis were completed. Results: We identified 73 [83%] dual-therapy patients, of whom 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse [log-rank test, p < 0.01]. Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of high-dose review periods [p = 0.67]; 3/52 [6%] low-dose patients and 3/21 [14%] high-dose patients [p = 0.34] discontinued MTX therapy due to adverse events. Conclusions: When combined with anti-TNF therapy, MTX at doses of > 12.5 mg/week was more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.