Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Kevin L. Winthrop, Jeffrey R. Curtis, Stephen Lindsey, Yoshiya Tanaka, Kunihiro Yamaoka, Hernan Valdez, Tomohiro Hirose, Chudy I. Nduaka, Lisy Wang, Alan M. Mendelsohn, Haiyun Fan, Connie Chen, Eustratios Bananis

Research output: Contribution to journalArticle

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Abstract

Objective: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. Methods: HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Results: Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95% CI 3.7-4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0-2.9) in Eastern Europe to 8.0 (95% CI 6.6-9.6) in Japan and 8.4 (95% CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Conclusion: Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.

Original languageEnglish
JournalArthritis and Rheumatology
DOIs
Publication statusAccepted/In press - 2017

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Herpes Zoster
Glucocorticoids
Confidence Intervals
Antirheumatic Agents
Incidence
Therapeutics
Rheumatoid Arthritis
tofacitinib
Eastern Europe
Korea
Proportional Hazards Models
Japan
Databases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Winthrop, K. L., Curtis, J. R., Lindsey, S., Tanaka, Y., Yamaoka, K., Valdez, H., ... Bananis, E. (Accepted/In press). Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. Arthritis and Rheumatology. https://doi.org/10.1002/art.40189

Herpes Zoster and Tofacitinib : Clinical Outcomes and the Risk of Concomitant Therapy. / Winthrop, Kevin L.; Curtis, Jeffrey R.; Lindsey, Stephen; Tanaka, Yoshiya; Yamaoka, Kunihiro; Valdez, Hernan; Hirose, Tomohiro; Nduaka, Chudy I.; Wang, Lisy; Mendelsohn, Alan M.; Fan, Haiyun; Chen, Connie; Bananis, Eustratios.

In: Arthritis and Rheumatology, 2017.

Research output: Contribution to journalArticle

Winthrop, KL, Curtis, JR, Lindsey, S, Tanaka, Y, Yamaoka, K, Valdez, H, Hirose, T, Nduaka, CI, Wang, L, Mendelsohn, AM, Fan, H, Chen, C & Bananis, E 2017, 'Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy', Arthritis and Rheumatology. https://doi.org/10.1002/art.40189
Winthrop, Kevin L. ; Curtis, Jeffrey R. ; Lindsey, Stephen ; Tanaka, Yoshiya ; Yamaoka, Kunihiro ; Valdez, Hernan ; Hirose, Tomohiro ; Nduaka, Chudy I. ; Wang, Lisy ; Mendelsohn, Alan M. ; Fan, Haiyun ; Chen, Connie ; Bananis, Eustratios. / Herpes Zoster and Tofacitinib : Clinical Outcomes and the Risk of Concomitant Therapy. In: Arthritis and Rheumatology. 2017.
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abstract = "Objective: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. Methods: HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95{\%} confidence intervals [95{\%} CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Results: Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95{\%} CI 3.7-4.4). In most cases (93{\%}), HZ was classified as nonserious, and the majority of patients (94{\%}) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95{\%} CI 2.0-2.9) in Eastern Europe to 8.0 (95{\%} CI 6.6-9.6) in Japan and 8.4 (95{\%} CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95{\%} CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95{\%} CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Conclusion: Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.",
author = "Winthrop, {Kevin L.} and Curtis, {Jeffrey R.} and Stephen Lindsey and Yoshiya Tanaka and Kunihiro Yamaoka and Hernan Valdez and Tomohiro Hirose and Nduaka, {Chudy I.} and Lisy Wang and Mendelsohn, {Alan M.} and Haiyun Fan and Connie Chen and Eustratios Bananis",
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T1 - Herpes Zoster and Tofacitinib

T2 - Clinical Outcomes and the Risk of Concomitant Therapy

AU - Winthrop, Kevin L.

AU - Curtis, Jeffrey R.

AU - Lindsey, Stephen

AU - Tanaka, Yoshiya

AU - Yamaoka, Kunihiro

AU - Valdez, Hernan

AU - Hirose, Tomohiro

AU - Nduaka, Chudy I.

AU - Wang, Lisy

AU - Mendelsohn, Alan M.

AU - Fan, Haiyun

AU - Chen, Connie

AU - Bananis, Eustratios

PY - 2017

Y1 - 2017

N2 - Objective: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. Methods: HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Results: Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95% CI 3.7-4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0-2.9) in Eastern Europe to 8.0 (95% CI 6.6-9.6) in Japan and 8.4 (95% CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Conclusion: Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.

AB - Objective: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. Methods: HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Results: Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95% CI 3.7-4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0-2.9) in Eastern Europe to 8.0 (95% CI 6.6-9.6) in Japan and 8.4 (95% CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Conclusion: Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.

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