Herpes Zoster in Tofacitinib: Risk is Further Increased with Glucocorticoids but not Methotrexate.

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. This article is protected by copyright. All rights reserved.