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Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis

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Abstract

Objective

Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).

Methods

Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported.

Results

After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline “pre-MTX” assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity.

Conclusion

Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs.

Key Points

• This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis.

• Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring.

• Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.

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Data availability

Data is available from the corresponding authors upon reasonable request.

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Acknowledgment

A Faulkner assisted with the search strategy.

Funding

This work was supported by a grant from the International League of Associations for Rheumatology (ILAR).

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Authors and Affiliations

  1. The Research Institute of the McGill University Health Centre, 1001 Decarie Blvd, Office # EM2-3238, Montreal, QC, H4A 3J1, Canada

    Valeria Valerio & Inés Colmegna

  2. Internal Medicine Residency Program, McGill University Health Centre, Montreal, QC, Canada

    Michelle Kwok

  3. Neil John Maclean Library, University of Manitoba, Winnipeg, Manitoba, Canada

    Hal Loewen & Janice Winkler

  4. Department of Rheumatology, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa

    Girish M. Mody

  5. Division of Rheumatology, Department of Pediatrics, McGill University, Montreal, QC, Canada

    Rosie Scuccimarri

  6. Thomas Jefferson University, Philadelphia, PA, USA

    Michele Meltzer

  7. Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia

    Yewondwossen Mengistu

  8. Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Candace H. Feldman & Michael E. Weinblatt

  9. Division of Rheumatology, University of British Columbia, Arthritis Research Canada, Vancouver, Canada

    Diane Lacaille

  10. Section of Rheumatology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    Carol A. Hitchon

  11. Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC, Canada

    Inés Colmegna

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  1. Valeria Valerio
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  2. Michelle Kwok
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Contributions

Carol A. Hitchon and Inés Colmegna equally contributed as leading authors to this work.

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Correspondence to Inés Colmegna.

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Valerio, V., Kwok, M., Loewen, H. et al. Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. Clin Rheumatol 40, 1259–1271 (2021). https://doi.org/10.1007/s10067-020-05363-2

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