{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:59Z","timestamp":1791976499782,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T00:00:00Z","timestamp":1527120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R219\u20102016\u2010270"],"award-info":[{"award-number":["R219\u20102016\u2010270"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Case reports and pharmacokinetic studies have suggested that concomitant use of low\u2010dose methotrexate and nonsteroidal anti\u2010inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low\u2010dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study was conducted as a register\u2010based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n\u00a0=\u00a021\u00a0536) and control episodes of use of methotrexate alone (n\u00a0=\u00a021\u00a0725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional\u2010hazards regression, with adjustment using inverse\u2010probability\u2010of\u2010treatment weighting based on propensity scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During follow\u2010up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person\u2010years) and 129 during control episodes (11.0 per 1000 person\u2010years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07\u20101.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Concomitant use of low\u2010dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low\u2010dose methotrexate and NSAID are coprescribed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4555","type":"journal-article","created":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T07:40:12Z","timestamp":1527147612000},"page":"885-893","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Concomitant use of low\u2010dose methotrexate and <scp>NSAIDs<\/scp> and the risk of serious adverse events among patients with rheumatoid arthritis"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-7215","authenticated-orcid":false,"given":"Henrik","family":"Svanstr\u00f6m","sequence":"first","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Melbye","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Medicine Stanford University School of Medicine  Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"},{"name":"Clinical Epidemiology Unit, Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8"},{"key":"e_1_2_11_3_1","first-page":"1","article-title":"2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"68","author":"Singh JA","year":"2015","journal-title":"Arthritis Rheumatol (Hoboken, NJ)"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204573"},{"issue":"6","key":"e_1_2_11_5_1","first-page":"CD000957","article-title":"Methotrexate for treating rheumatoid arthritis","author":"Lopez\u2010Olivo MA","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630030-00002"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1993.tb04158.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2014.01.014"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009749609065644"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.093690"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/ar4174","article-title":"Use of NSAIDs in treating patients with arthritis","volume":"15","author":"Crofford LJ","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90786-5"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.11.57"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.121491"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028016672035"},{"key":"e_1_2_11_16_1","first-page":"1","article-title":"Preventing and managing toxicities of high\u2010dose methotrexate","author":"Howard SC","year":"2016","journal-title":"Oncologist"},{"key":"e_1_2_11_17_1","first-page":"1061","article-title":"Adverse drug reactions and drug\u2010drug interactions with over\u2010the\u2010counter NSAIDs","volume":"11","author":"Moore N","year":"2015","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090153"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120345"},{"key":"e_1_2_11_20_1","unstructured":"Dava Pharmaceuticals Inc.Rheumatrex revised January2016. 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