{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:53:42Z","timestamp":1790538822846,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Tofacitinib is an oral <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content> inhibitor indicated for the treatment of rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). We characterized lymphoma events in the tofacitinib <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> clinical development program.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, 6 phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>, and 2 long\u2010term extension) of patients with moderate to severe <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>. Patients in these studies received tofacitinib dosed at 1\u201330 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease\u2010modifying antirheumatic drugs. Lymphoma incidence rates (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>s; number of patients with events\/100 patient\u2010years) and standardized incidence ratios (<jats:styled-content style=\"fixed-case\">SIR<\/jats:styled-content>s) were calculated. A descriptive case\u2013matched control analysis (1:4) was performed to identify potential risk factors for lymphoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 6,194 patients received tofacitinib (19,406 patient\u2010years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> 0.10 [95% confidence interval (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) 0.06\u20130.15]), with no increase observed with time of exposure. The age\u2010 and sex\u2010adjusted <jats:styled-content style=\"fixed-case\">SIR<\/jats:styled-content> of lymphoma was 2.62 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.58\u20134.09) (Surveillance, Epidemiology, and End Results [<jats:styled-content style=\"fixed-case\">SEER<\/jats:styled-content>] program database). The clinical characteristics of the 19 lymphomas were typical for the <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> population. Three lymphomas were positive for Epstein\u2010Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sj\u00f6gren's syndrome and were positive for anti\u2013cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the tofacitinib <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.23421","type":"journal-article","created":{"date-parts":[[2017,9,21]],"date-time":"2017-09-21T10:23:02Z","timestamp":1505989382000},"page":"685-694","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program"],"prefix":"10.1002","volume":"70","author":[{"given":"Xavier","family":"Mariette","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris\u2010Sud, Assistance publique\u2013H\u00f4pitaux de Paris H\u00f4pitaux Universitaires Paris\u2010Sud INSERM U1184 Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Chen","sequence":"additional","affiliation":[{"name":"Pfizer Inc. New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Biswas","sequence":"additional","affiliation":[{"name":"Pfizer Inc. New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Kwok","sequence":"additional","affiliation":[{"name":"Pfizer Inc. New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary G.","family":"Boy","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 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