OBJECTIVE: Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids. METHODS: Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (±7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates. RESULTS: We studied 8,030 new tofacitinib users (83.3% women). The mean ± SD age was 60.3 ± 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk. CONCLUSION: In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.
OBJECTIVE: Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids. METHODS: Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (±7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates. RESULTS: We studied 8,030 new tofacitinib users (83.3% women). The mean ± SD age was 60.3 ± 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk. CONCLUSION: In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.
Authors: Gerd R Burmester; Peter Nash; Bruce E Sands; Kim Papp; Lori Stockert; Thomas V Jones; Huaming Tan; Ann Madsen; Hernan Valdez; Stanley B Cohen Journal: RMD Open Date: 2021-05
Authors: Peter Nash; Andreas Kerschbaumer; Thomas Dörner; Maxime Dougados; Roy M Fleischmann; Klaus Geissler; Iain McInnes; Janet E Pope; Désirée van der Heijde; Michaela Stoffer-Marx; Tsutomu Takeuchi; Michael Trauner; Kevin L Winthrop; Maarten de Wit; Daniel Aletaha; Xenofon Baraliakos; Wolf-Henning Boehncke; Paul Emery; John D Isaacs; Joel Kremer; Eun Bong Lee; Walter P Maksymowych; Marieke Voshaar; Lai-Shan Tam; Yoshiya Tanaka; Filip van den Bosch; René Westhovens; Ricardo Xavier; Josef S Smolen Journal: Ann Rheum Dis Date: 2020-11-06 Impact factor: 19.103
Authors: Stanley B Cohen; Yoshiya Tanaka; Xavier Mariette; Jeffrey R Curtis; Eun Bong Lee; Peter Nash; Kevin L Winthrop; Christina Charles-Schoeman; Lisy Wang; Connie Chen; Kenneth Kwok; Pinaki Biswas; Andrea Shapiro; Ann Madsen; Jürgen Wollenhaupt Journal: RMD Open Date: 2020-10