{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:59:28Z","timestamp":1787140768899,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T00:00:00Z","timestamp":1146096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease\u2010modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population\u2010based epidemiologic study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case\u2013control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1\u20133.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4\u20133.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2\u20135.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The reports of ILD associated with leflunomide use are likely the result of channeling of high\u2010risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.21806","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T13:03:33Z","timestamp":1146143013000},"page":"1435-1439","source":"Crossref","is-referenced-by-count":147,"title":["Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis"],"prefix":"10.1002","volume":"54","author":[{"given":"Samy","family":"Suissa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,4,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200109)44:9<1984::AID-ART346>3.0.CO;2-B"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15527-X"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-005-0387-9"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780401016"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg466"},{"key":"e_1_2_6_7_2","volume-title":"PharMetrics patient\u2010centric database","year":"2005"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.02.032"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh610"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470842555.ch44"},{"key":"e_1_2_6_11_2","volume-title":"Modern epidemiology","author":"Rothman KJ","year":"1998"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11015"},{"key":"e_1_2_6_13_2","unstructured":"GoldkindL SimonLS. FDA meeting March 2003: update on the safety of new drugs for rheumatoid arthritis. Part III. Safety and efficacy update on leflunomide (Arava). URL:http:\/\/www.rheumatology.org\/publications\/hotline\/0503leffda.asp?aud=mem."},{"key":"e_1_2_6_14_2","first-page":"1906","article-title":"Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study of leflunomide compared with other DMARD","volume":"31","author":"Cannon GW","year":"2004","journal-title":"J Rheumatol"},{"issue":"9","key":"e_1_2_6_15_2","first-page":"S341","article-title":"Methotrexate\u2010induced pulmonary disease during treatment of rheumatoid arthritis in large clinical trials","volume":"43","author":"Cannon GW","year":"2000","journal-title":"Arthritis Rheum"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.21806","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.21806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T03:26:51Z","timestamp":1696994811000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.21806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4,27]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,5]]}},"alternative-id":["10.1002\/art.21806"],"URL":"https:\/\/doi.org\/10.1002\/art.21806","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.14216.471718","asserted-by":"object"}]},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,4,27]]}}}