SynthesisFrontiers in immunology2026
Subcutaneous methotrexate compared with oral methotrexate in rheumatoid arthritis: a systematic review and meta-analysis.
Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
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Authors and funding
5 authors.
Funding
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Abstract
Objectives: To integrate evidence from randomized controlled trials (RCTs) comparing subcutaneous (SC) and oral methotrexate (MTX) for rheumatoid arthritis (RA) to provide optimal clinical treatment strategies. Methods: This meta-analysis conducted comprehensive search of PubMed, Web of Science, Embase and Cochrane Library, retrieving all relevant RCTs published up to June 18, 2025. Random-effects models were utilized to calculate the relative risk (RR), mean difference (MD) and their 95% confidence intervals (CIs), to evaluate efficacy and safety between subcutaneous injections and oral administration of MTX. Results: A total of 1,034 articles were retrieved, and 9 RCTs that met the criteria were ultimately included, involving 974 RA patients in total. In the primary random-effects analyses, compared to oral MTX, subcutaneous MTX increased the ACR20 response rate (RR = 1.15; 95%CI: 1.05, 1.25), increased the ACR50 response rate (RR = 1.14; 95%CI: 1.01, 1.29), and reduced the incidence of gastrointestinal (GI)-related adverse event (AE) (RR = 0.58; 95%CI: 0.40, 0.83) and diarrhea (RR = 0.42; 95%CI: 0.21, 0.84). Fixed-effect sensitivity analyses supported the ACR20 and GI-related safety findings, but the ACR50 result was attenuated. Subcutaneous MTX did not show statistically significant differences in ACR70 response rate, DAS28-ESR score, bioavailability area under the curve, C Conclusion: Compared with oral administration, subcutaneous MTX was associated with a higher ACR20 response and lower GI-related AE and diarrhea in the primary random-effects analyses. These findings suggested that subcutaneous MTX may be an effective and generally well-tolerated option, particularly for patients with inadequate response or poor gastrointestinal tolerability to oral MTX, while evidence for ACR50, ACR70, DAS28-ESR and bioavailability remains less certain.
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