Optimizing methotrexate therapy in rheumatoid arthritis: a systematic literature review

Joint Bone Spine. 2011 Dec;78(6):587-92. doi: 10.1016/j.jbspin.2011.01.010. Epub 2011 Mar 27.


Objective: To describe the means of optimizing methotrexate therapy for rheumatoid arthritis in daily clinical practice, based on a systematic literature review.

Methods: We systematically reviewed the literature by searching the PubMed, Embase, and Cochrane databases and reviewing communications to ACR and EULAR meetings for studies on methotrexate starting dosages, dosage increment sizes and intervals, maximum dosages, and routes of administration in patients with rheumatoid arthritis. We used an appropriate scoring system to assess the methodological quality of each selected study.

Results: We identified 519 studies of which 11 were selected based on the titles and abstracts then on the full-length articles. Methotrexate was optimally effective when started in a high dosage (more than 10mg/week orally) that was subsequently increased by 5mg/month up to 25-30mg/week,(1) with appropriate adjustments based on clinical disease activity and tolerance of each patient. For a given methotrexate dosage, parenteral administration was more effective and produced fewer gastrointestinal adverse effects than oral administration.

Conclusion: The information supplied by this systematic review support higher starting dosage, an intensive dosage increase schedule and recourse to parenteral administration in case of unresponsiveness or intolerance to oral methotrexate. They should improve the management of patients given methotrexate therapy for rheumatoid arthritis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Infusions, Subcutaneous
  • Methotrexate / administration & dosage*
  • Methotrexate / therapeutic use*
  • Treatment Outcome


  • Antirheumatic Agents
  • Methotrexate