Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids

Jeffrey R. Curtis, Fenglong Xie, Shuo Yang, Sasha Bernatsky, Lang Chen, Huifeng Yun, Kevin Winthrop

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1249-1254
Number of pages6
JournalArthritis Care and Research
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2019

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Herpes Zoster
Methotrexate
Glucocorticoids
Rheumatoid Arthritis
Incidence
Vaccination
tofacitinib
Confidence Intervals
International Classification of Diseases
Medicare
Antiviral Agents
Demography

ASJC Scopus subject areas

  • Rheumatology

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Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids. / Curtis, Jeffrey R.; Xie, Fenglong; Yang, Shuo; Bernatsky, Sasha; Chen, Lang; Yun, Huifeng; Winthrop, Kevin.

In: Arthritis Care and Research, Vol. 71, No. 9, 01.09.2019, p. 1249-1254.

Research output: Contribution to journalArticle

Curtis, Jeffrey R. ; Xie, Fenglong ; Yang, Shuo ; Bernatsky, Sasha ; Chen, Lang ; Yun, Huifeng ; Winthrop, Kevin. / Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids. In: Arthritis Care and Research. 2019 ; Vol. 71, No. 9. pp. 1249-1254.
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abstract = "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.",
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T1 - Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids

AU - Curtis, Jeffrey R.

AU - Xie, Fenglong

AU - Yang, Shuo

AU - Bernatsky, Sasha

AU - Chen, Lang

AU - Yun, Huifeng

AU - Winthrop, Kevin

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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