{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:24:49Z","timestamp":1789917889814,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006264","name":"RIKEN","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis, and has been previously investigated for psoriasis (PsO). This meta\u2010analysis of genome\u2010wide association studies (GWAS) was performed to identify genetic factors associated with increased risk\/faster onset of herpes zoster (HZ) in subjects with RA or PsO receiving tofacitinib treatment, and to determine potential mechanisms that could be attributed to the varying rates of HZ across ethnicities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In an ethnicity\/indication\u2010specific, trans\u2010ethnic, trans\u2010population meta\u2010analysis of GWAS in subjects with RA or PsO from phase II, phase III, and long\u2010term extension studies of tofacitinib, 8\u00a0million genetic variants were evaluated for their potential association with time to an HZ event and incidence of an HZ event (case versus control) with tofacitinib treatment, using Cox proportional hazard and logistic regression analyses, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 5,246 subjects were included (3,168 with RA and 2,078 with PsO). After adjustment for age, baseline absolute lymphocyte count, genetically defined ethnicity, and concomitant methotrexate use (in RA\u00a0subjects only), 4 loci were significantly associated with faster onset of HZ in European subjects (<jats:italic>P<\/jats:italic> &lt; 5 \u00d7 10<jats:sup>\u22128<\/jats:sup>), including a single\u2010nucleotide polymorphism (SNP) near <jats:italic>CD83<\/jats:italic> (frequency of risk allele ~2% in European subjects versus ~0.1% in East Asian subjects). In the trans\u2010ethnic, trans\u2010population meta\u2010analysis, the <jats:italic>CD83<\/jats:italic> SNP remained significant. Four additional significant loci were identified in the meta\u2010analysis, among which a SNP near <jats:italic>IL17RB<\/jats:italic> was associated with faster onset of HZ (meta\u2010analysis hazard ratio 3.6 [95%\u00a0confidence interval 2.40\u20135.44], <jats:italic>P<\/jats:italic> = 7.6 \u00d7 10<jats:sup>\u221210<\/jats:sup>; frequency of risk allele ~12% in East Asian subjects versus &lt;0.2% in European subjects).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic analysis of tofacitinib\u2010treated subjects with RA or PsO identified multiple loci associated with increased HZ risk. Prevalent variants near the immune\u2010relevant genes <jats:italic>CD83<\/jats:italic> and <jats:italic>IL17RB<\/jats:italic> in European and East Asian populations, respectively, may contribute to risk of HZ in tofacitinib\u2010treated subjects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41655","type":"journal-article","created":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T05:43:16Z","timestamp":1610862196000},"page":"1155-1166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Contribution of a European\u2010Prevalent Variant near <i>CD83<\/i> and an East Asian\u2013Prevalent Variant near <i>IL17RB<\/i> to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome\u2010Wide Association Study Meta\u2010Analyses"],"prefix":"10.1002","volume":"73","author":[{"given":"Nan","family":"Bing","sequence":"first","affiliation":[{"name":"Pfizer  Cambridge 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Ishigaki","sequence":"additional","affiliation":[{"name":"Center for Integrative Medical Sciences, RIKEN  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Sumitomo","sequence":"additional","affiliation":[{"name":"University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Fujio","sequence":"additional","affiliation":[{"name":"University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pfizer  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hernan","family":"Valdez","sequence":"additional","affiliation":[{"name":"Pfizer  New York New 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