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Oral methotrexate at doses 15–25 mg/week is non-inferior to parenteral regarding efficacy and safety in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

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Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

The most optimal route of methotrexate (MTX) administration for the treatment of rheumatoid arthritis (RA) has not yet been established. Our aim was to compare the efficacy, safety, and bioavailability profiles of oral MTX with parenteral MTX in adult patients with RA.

Methods

PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalKey were searched for published randomized trials through December 30, 2021. Random-effects models were used to assess pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs). This review was registered in PROSPERO (number CRD42022297810).

Results

Of 705 identified trials, 6 met the criteria and were included in our meta-analysis (644 subjects). Compared to parenteral MTX, oral MTX yielded no significant differences in response rates of 20% (OR: 0.68; 95% CI: 0.40–1.75), 50% (OR: 0.75; 95% CI: 0.44–1.28), and 70% (OR: 0.75; 95% CI: 0.51–1.09) improvement according to American College of Rheumatology criteria (ACR20/50/70 response), and no increased relative risk of any adverse event (OR: 1.20; 95% CI: 0.49–2.93). Furthermore, parenteral MTX showed a significant advantage in the value of AUC0-t (MD: − 536.36; 95% CI: − 1054.22 to − 18.50), but not in Cmax (MD: − 12.86; 95% CI: − 84.30 to 58.58) and Tmax (MD: − 0.31; 95% CI: − 0.70 to 0.08) compared with oral MTX.

Conclusion

Oral MTX at doses of 15–25 mg/week in active RA is not inferior to parenteral regarding efficacy and safety. This supports the initial therapy with oral MTX.

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Acknowledgements

Thank you for all the participants in this study.

Author information

Author notes

  1. Fang Wang and Jingliang Tang contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Fang Wang

  2. School of Ethnic Medicine, State Ethnic Affairs Commission & Ministry of Education, Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming, 650500, Yunnan, People’s Republic of China

    Jingliang Tang, Yanyan Qi, Ganpeng Li & Fang Wang

  3. Department of Neonatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250100, People’s Republic of China

    Zhe Li

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  1. Fang Wang
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Contributions

FW and JLT designed the study. FW, JLT, and ZL selected studies for inclusion and abstracted data. FW and JLT analyzed data. FW, JLT, and ZL did the data interpretation. FW and JLT wrote the manuscript. The final manuscript was approved by all authors.

Corresponding authors

Correspondence to Jingliang Tang or Fang Wang.

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The authors declare no competing interests.

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Key Points.

• The most optimal route of MTX administration for the treatment of RA has not yet been established.

• The results of this meta-analysis showed oral MTX is not inferior to parenteral regarding efficacy and safety in RA.

• Further comparison of the bioavailability of MTX between oral and parenteral administration showed similar results.

• Together with higher costs and burden of regular injections of parenteral MTX, oral MTX should be preferred for the initial prescribing of MTX.

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Wang, F., Tang, J., Li, Z. et al. Oral methotrexate at doses 15–25 mg/week is non-inferior to parenteral regarding efficacy and safety in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol 41, 2701–2712 (2022). https://doi.org/10.1007/s10067-022-06221-z

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  • DOI: https://doi.org/10.1007/s10067-022-06221-z

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