{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:09:01Z","timestamp":1784268541149,"version":"3.55.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u00a0=\u00a01.15; 95%CI: 1.05, 1.25), increased the ACR50 response rate (RR\u00a0=\u00a01.14; 95%CI: 1.01, 1.29), and reduced the incidence of gastrointestinal (GI)-related adverse event (AE) (RR\u00a0=\u00a00.58; 95%CI: 0.40, 0.83) and diarrhea (RR\u00a0=\u00a00.42; 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\n                      <jats:sub>max<\/jats:sub>\n                      , or the incidence of other AE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1816269","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:45:27Z","timestamp":1784267127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Subcutaneous methotrexate compared with oral methotrexate in rheumatoid arthritis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Guangtao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16915","article-title":"EuroGuiDerm guideline on the systemic treatment of psoriasis vulgaris - 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