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

Abstract

Background Increased herpes zoster (HZ) has been observed with janus kinase inhibitors such as tofacitinib. However, it is unclear whether concomitant methotrexate (MTX) and/or glucocorticoids (GC) confer additional (additive or multiplicative) risk. We evaluated HZ risk in tofacitinib users with and without MTX and GC. Methods Within MarketScan and Medicare data (2011‐2016) we identified all rheumatologist‐diagnosed RA patients initiating tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to index date. HZ was ascertained using ICD9/10 codes with anti‐viral drug use (+‐7 days). Multivariable (MV) Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and GC, controlling for baseline covariates. Results We studied 8,030 new tofacitinib users (83.3% women). Mean (SD) age was 60.3 (12.6) years. HZ incidence in tofacitinib users was numerically lowest in the absence of GC (3.4/100py with MTX; 3.7/100py without MTX). An approximately two‐fold increased incidence of HZ was observed for tofacitinib users receiving either GCs alone (6.0/100 py) or both MTX+GCs (6.5/100py). The adjusted HR for HZ in tofacitinib users was unchanged (HR=0.99, 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+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 GC exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.