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

Abstract

ObjectivePatients 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.MethodsHZ 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.ResultsAcross 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.ConclusionPatients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

“…One infectious complication that is more common in tofacitinib and baricitinib treated patients than patients treated with biologics is reactivation of varicella zoster virus (VZV; herpes zoster) . RA itself represents an independent risk factor for reactivation of VZV, followed by age and the use of prednisone, and the risk of herpes zoster infections in patients treated with tofacitinib is further increased by concomitant use of steroids and methotrexate .…”

Tofacitinib y la necesidad de vigilancia de potenciales efectos adversos en pacientes con artritis reumatoide

“…Además se señalaba que la edad mayor de 65 años, el uso de glucocorticoides y la dosis de tofacitinib fueron factores de riesgo independientes para la aparición de HZ. [3] En relación con la protección que conferiría la vacunación específica contra el virus de la varicela zoster (VVZ), un ensayo clínico en fase II controlado con placebo que incluyó a 112 pacientes mayores de 50 años con AR activa y que recibían metotrexato de terapia de base, se administró la vacunación a todos los casos incluidos, aleatorizándose un grupo que recibió tofacitinib y otro placebo; llegándose a determinar a las 6 semanas los niveles de IgG específicos de VVZ, sin encontrar diferencias estadísticamente significativas de los niveles de anticuerpos entre ambos grupos y manteniendo respuestas inmunomediadas humorales y celulares similares. [4] …”

Live Zoster Vaccine in Patients With Rheumatoid Arthritis Treated With Tofacitinib With or Without Methotrexate, or Adalimumab With Methotrexate: A Post Hoc Analysis of Data From a Phase IIIb/IV Randomized Study

“…Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Tofacitinib has been reported to increase HZ risk in patients with RA, and the risk is higher still in older patients, those receiving corticosteroids , and in certain Asian populations, particularly Japanese and Korean patients . In an analysis of data from phase II, phase III, and long‐term extension (LTE) studies in patients with RA who received tofacitinib 5 or 10 mg twice daily (BID) without prior LZV (per protocol, some patients may have received LZV), the HZ incidence rate (IR) was 4.4 per 100 patient‐years (95% confidence interval [95% CI] 3.8–4.9) globally and 9.2 per 100 patient‐years (95% CI 7.5–11.4) in Japan/Korea .…”

“…In an analysis of data from phase II, phase III, and long‐term extension (LTE) studies in patients with RA who received tofacitinib 5 or 10 mg twice daily (BID) without prior LZV (per protocol, some patients may have received LZV), the HZ incidence rate (IR) was 4.4 per 100 patient‐years (95% confidence interval [95% CI] 3.8–4.9) globally and 9.2 per 100 patient‐years (95% CI 7.5–11.4) in Japan/Korea . Analysis of phase I, phase II, phase III, and LTE study data showed that most HZ events in tofacitinib‐treated patients with RA were not serious (per the investigator's assessment) and resolved with standard antiviral treatment . Increased HZ risk versus placebo has also been observed with another Janus kinase inhibitor, baricitinib, in an analysis of data pooled from phase I, phase II, phase III, and LTE studies.…”