Optimal doses of methotrexate combined with anti-TNF therapy to maintain clinical remission in inflammatory bowel disease.

Abstract

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 ≤ 12.5mg/week and high-dose MTX as 15-25mg/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 >12.5mg/week was more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.

• Authors: Ruben J Colman, David T Rubin
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 9 Issue 4 Pg. 312-7 (Apr 2015) ISSN: 1876-4479 [Electronic] England
• PMID: 25616487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Anti-Inflammatory Agents
• Gastrointestinal Agents
• Immunosuppressive Agents
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab
• Methotrexate

Topics

• Adalimumab (administration & dosage)
• Adolescent
• Adult
• Anti-Inflammatory Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Gastrointestinal Agents (administration & dosage)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Inflammatory Bowel Diseases (drug therapy)
• Infliximab (administration & dosage)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Remission Induction
• Retrospective Studies
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Young Adult