{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T20:11:54Z","timestamp":1783368714769,"version":"3.54.6"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs\/LSCs and incidence rates (patients with events\/100 patient-years) of SIEs and HZ were analysed over 75\u2009months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Median ALCs were generally stable over 75\u2009months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36\u201375. SIE\/HZ incidence rates were higher in patients with ALC &amp;lt;0.5\u2009\u00d7\u2009103 cells\/mm3 versus those with ALC \u22650.5\u2009\u00d7\u2009103 cells\/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with\/without SIEs or HZ events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>SIE\/HZ risk was highest in patients with ALC &amp;lt;0.5\u2009\u00d7\u2009103 cells\/mm3, supporting this threshold as clinically relevant for defining increased SIE\/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mr\/roae030","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T16:32:11Z","timestamp":1716827531000},"page":"1115-1124","source":"Crossref","is-referenced-by-count":1,"title":["Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"first","affiliation":[{"name":"The First Department of Internal Medicine, University of Occupational and Environmental Health , Kitakyushu,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hernan","family":"Valdez","sequence":"additional","affiliation":[{"name":"Pfizer Inc , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Collinge","sequence":"additional","affiliation":[{"name":"Pfizer Inc , Groton, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel H","family":"Zwillich","sequence":"additional","affiliation":[{"name":"Pfizer Inc , Groton, CT,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Toyoizumi","sequence":"additional","affiliation":[{"name":"Pfizer R&D Japan G.K. , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Kwok","sequence":"additional","affiliation":[{"name":"Pfizer Inc , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9569-6834","authenticated-orcid":false,"given":"Tomohiro","family":"Hirose","sequence":"additional","affiliation":[{"name":"Pfizer Japan Inc , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"2024110410413134300_R1","doi-asserted-by":"crossref","first-page":"i70","DOI":"10.1136\/annrheumdis-2011-200595","article-title":"In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis","volume":"71","author":"Tanaka","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"2024110410413134300_R2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/jb\/mvv069","article-title":"Recent progress and perspective in JAK inhibitors for rheumatoid arthritis: from bench to bedside","volume":"158","author":"Tanaka","year":"2015","journal-title":"J Biochem"},{"key":"2024110410413134300_R3","doi-asserted-by":"crossref","DOI":"10.1186\/1476-9255-7-41","article-title":"Anti-inflammatory activity and neutrophil\nreductions mediated by the JAK1\/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis","volume-title":"J Inflamm (Lond)","author":"Meyer","year":"2010"},{"key":"2024110410413134300_R4","article-title":"Characterization of a potent inhibitor of JAK kinases, CP-690,550, and inhibition of specific JAK\/STAT pathways at efficacious exposures in a rodent model of arthritis","volume-title":"At: Inflammation Research Association, 15th International Conference","author":"Li"},{"key":"2024110410413134300_R5","article-title":"Xeljanz\u00ae (tofacitinib): summary of product characteristics","author":"European Medicines Agency","year":"2022"},{"key":"2024110410413134300_R6","first-page":"318","article-title":"The mechanism of action of tofacitinib - an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis","volume":"34","author":"Hodge","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"2024110410413134300_R7","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1002\/art.24567","article-title":"The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo","volume":"60","author":"Kremer","year":"2009","journal-title":"Arthritis Rheum"},{"key":"2024110410413134300_R8","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/acr.20494","article-title":"Tofacitinib study investigators. 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