TY - JOUR
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
N1 - Funding Information:
Supported by Pfizer.
Funding Information:
Dr. Winthrop has received consulting fees (more than $10,000) and research grants from Pfizer. Dr. Curtis has received consulting fees (more than $10,000) and research grants from Pfizer. Dr. Lindsey has received speaking fees (less than $10,000) from Pfizer. Dr. Tanaka has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Pfizer. Dr. Yamaoka has received consulting fees and speaking fees (more than $10,000) from Pfizer. Drs. Valdez, Nduaka, Wang, Mendelsohn, Chen, and Bananis, and Mr. Hirose and Ms Fan own stock or stock options in Pfizer Inc.
Funding Information:
This study was sponsored by Pfizer Inc. The manuscript was drafted, under direction from the authors, by Alice MacLachlan at Complete Medical Communications, funded by Pfizer Inc., with all authors providing subsequent critical revision. All authors interpreted the results, approved the final draft, and had the final decision to submit the manuscript for publication. Pfizer Inc. did not control the analysis or interpretation of the study results. Publication of this article was not contingent upon approval by Pfizer Inc.
Publisher Copyright:
© 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
PY - 2017/10
Y1 - 2017/10
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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U2 - 10.1002/art.40189
DO - 10.1002/art.40189
M3 - Article
C2 - 28845604
AN - SCOPUS:85028916794
SN - 2326-5191
VL - 69
SP - 1960
EP - 1968
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 10
ER -