Objective
To evaluate the risks of herpes zoster (HZ) and herpes simplex virus
infection (HSV) associated with tofacitinib compared to biologic agents
among patients with rheumatoid arthritis (RA).
Methods
Using health plan data from 2010–2014, RA patients initiating
tofacitinib or biologics with no history of HZ or HSV were identified.
Incident cases of HZ or HSV within this cohort were identified. Crude
incidence rates were calculated by drug exposure. Cox proportional hazards
models evaluated the adjusted association between tofacitinib and HZ, and a
composite outcome of HZ or HSV.
Results
A total of 2,526 patients initiating tofacitinib were compared with
initiations of other biologics: anti-TNF (n=42,850), abatacept
(n=12,305), rituximab (n=5,078), and tocilizumab
(n=6,967). Tofacitinib patients were somewhat younger (mean age 55
years) versus those on other biologics, and somewhat less likely to use
concomitant MTX (39% vs. 43–56%, depending on
drug).
Crude incidence of HZ associated with tofacitinib was 3.87/100py.
After multivariable adjustment, HZ risk was significantly elevated, hazard
ratio [HR] 2.01 (95%CI 1.40–2.88) compared
to abatacept. Rates and adjusted HRs for all other RA biologics were
comparable to each other and abatacept. Older age, female sex, prednisone
>7.5mg/day, prior outpatient infection, and greater number of
hospitalizations were also associated with increased HZ risk Incidence rates
for the combined outcome were greatest for tofacitinib (7.61/100py) and
significantly elevated after adjustment (HR=1.40, 95%CI
1.09–1.81).
Conclusion
The rate of zoster associated with tofacitinib was approximately
double that observed in patients using biologics.