Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis

Abstract

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.

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

“…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 . A comparison of RA patients treated with tofacitinib versus other biological therapies showed that the rate of zoster associated with tofacitinib was approximately double that was observed in patients using biologics . The exact mechanism by which VZV reactivation occurs in the context of JAK inhibition is unclear; however, inhibition of antiviral actions mediated by interferon signaling would seem a likely explanation.…”

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo‐controlled phase 3 trial

“…Although there has been some controversy around the level of HZ risk associated with biologics for inflammatory disease, there appears to be strong evidence suggesting an increased risk with monoclonal tumor necrosis factor‐α inhibitors, and particularly with infliximab . However, an analysis of US health plan data suggested that the HZ risk associated with tofacitinib in rheumatoid arthritis patients was approximately double that with biologics . An increased incidence of HZ infection in Japanese patients receiving biologic treatment for psoriasis, above that observed in the general population, has also been reported …”

Managing varicella zoster virus contact and infection in patients on anti-rheumatic therapy

“…Preliminary data from phase II and III randomised controlled trials of the Janus Kinase (JAK) inhibitor tofacitinib in RA have shown an increased risk of uncomplicated zoster [34], recently estimated as double that of other biologics [35].…”