{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:28:10Z","timestamp":1788672490680,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To show the safety and efficacy of subcutaneous (SC) methotrexate (MTX) compared to oral MTX, alternative disease\u2010modifying antirheumatic drugs (DMARDs) monotherapy, biologic monotherapy, and combinations (conventional and biologic combination groups) in routine clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and laboratory data were retrospectively analyzed for rheumatology clinic attendances at a large Northeast England hospital trust between January 2014 and January 2018. Rates of adverse events and stop events (transaminitis [serum alanine aminotransferase level of &gt;80 units\/liter] or neutropenia [neutrophil count of &lt;2.0 \u00d7 10<jats:sup>9<\/jats:sup>\/liter]) were calculated, with adjustment for duration of DMARD exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the present study, 8,394 patients received DMARDs, with 2,093 patients receiving oral MTX and 949 patients receiving SC MTX. The median dose was 15 mg (interquartile range [IQR] 10\u201320 mg) for oral MTX, and 20 mg (IQR 15\u201325 mg) for SC MTX (<jats:italic>P<\/jats:italic> &lt; 0.0001). Continuation rates were higher for SC MTX therapy when adjusted for follow\u2010up duration, with a rate ratio (RR) of 1.54 (95% confidence interval [95% CI] 1.40\u20131.70) (<jats:italic>P<\/jats:italic> &lt; 0.0001). For the time period assessed, 2,382 patients experienced 4,358 adverse events, with 1,711 incidents of transaminitis and 2,647 incidents of neutropenia recorded. Significantly fewer adverse events were observed in patients who received SC MTX monotherapy versus those who received biologic and combination DMARD therapies (<jats:italic>P<\/jats:italic> &lt; 0.01). Compared to oral MTX, SC MTX was associated with a nonsignificant trend toward lower rates of neutropenia, but only a slightly higher rate of transaminitis (RR 1.26 [95% CI 1.07\u20131.48]) (<jats:italic>P<\/jats:italic> = 0.006), despite significantly higher doses of MTX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Subcutaneous MTX is safe in routine clinical practice. This is the largest study yet reported on SC MTX and provides observational data that SC MTX is continued longer and better tolerated in patients compared to other therapy groups, especially oral MTX.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.24334","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T08:52:44Z","timestamp":1590915164000},"page":"1306-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8305-3850","authenticated-orcid":false,"given":"Christien K. H.","family":"Li","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-2911","authenticated-orcid":false,"given":"Kenneth","family":"Baker","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-7373","authenticated-orcid":false,"given":"Tania","family":"Jones","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Coulson","sequence":"additional","affiliation":[{"name":"Northumbria Healthcare NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Roberts","sequence":"additional","affiliation":[{"name":"Therapy Audit Ltd  Shrewsbury UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-6155","authenticated-orcid":false,"given":"Fraser","family":"Birrell","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University and Northumbria Healthcare NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24038"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207524"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.094474"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201162"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22944"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-014-2546-x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0486-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23152"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206504"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205228"},{"key":"e_1_2_7_12_1","first-page":"483","article-title":"Comparative efficacy of subcutaneous versus oral methotrexate in active rheumatoid arthritis","volume":"22","author":"Islam MS","year":"2013","journal-title":"Mymensingh Med J"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.7861\/futurehosp.6-1-8"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00347-5"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16676-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23144"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.09.027"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h1046"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23830"}],"container-title":["Arthritis Care &amp; 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