Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: A meta-analysis

Andreea M Bujor, Sahar Janjua, Michael P LaValley, Josefina Duran, Jürgen Braun, David T Felson, Andreea M Bujor, Sahar Janjua, Michael P LaValley, Josefina Duran, Jürgen Braun, David T Felson

Abstract

Objective: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA.

Methods: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy).

Results: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events.

Conclusion: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents.

Conflict of interest statement

We have read the journal’s policy and the authors of the manuscript have the following competing interests: Dr. Jürgen’s original research was supported by funding from Medac GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow chart of study selection.
Fig 1. Flow chart of study selection.
Fig 2. Summary OR for achieving ACR20…
Fig 2. Summary OR for achieving ACR20 using parenteral vs. oral MTX.
Fig 3. Summary OR for adverse effects…
Fig 3. Summary OR for adverse effects data (any AE).
Fig 4. Summary OR for adverse effects…
Fig 4. Summary OR for adverse effects data.

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