Herpes Zoster Infection Most Often Associated with Tofacitinib


Tofacitinib associated with double the rate of herpes zoster infection as compared to other biologics.

Among individuals with rheumatoid arthritis (RA), those who take tofacitinib experience double the rate of associated herpes zoster (HZ) than individuals taking other biologics.

According to an April Annuals of Rheumatic Disease study, entitled, “Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis,” researchers from the University of Alabama at Birmingham determined the rate of herpes zoster  infection is substantially higher among patients who take tofacitinib than those who take infliximab, tocilizumab and abatacept, or rituximab.

Tofacitinib, a small molecule used to treat rheumatoid arthritis has immunomodulatory effects, mainly inhibits janus kinase (JAK) 1/3 kinases. Almost all tofacitinib data is based on placebo-based trials, so its real-world safety and comparability with biologics, relating to herpes simplex virus and herpes simplex virus (HSV), is unknown. Existing research does show, however, that rheumatoid arthritis patients have an elevated herpes zoster risk compared to the general population.

“Our analysis is the first real-world evaluation of HZ risk involving tofacitinib and biologic therapies simultaneously, while controlling for other HZ risk factors,” researchers wrote. “Our observations are consistent with the conclusions from the tofacitinib clinical trial experience and provide real-world comparative evidence.”

It’s unclear how tofacitnib causes HZ, but cell-mediated immunity is important in controlling the varicella virus. Patients with waning VZV-specific CD4 T-cell function also have a high HZ risk. Researchers also said one potential explanation is that tofacitnib diminishes CD4 T-cell proliferation and subsequent interferon-Ɣ production.

Based on this study’s results, tofacitinib patients were slightly younger at 55 years old than biologics patients. They were also somewhat less likely than biologics patients to use concomitant methotrexate – 39 percent versus 43 to 56 percent.

Investigators used Cox proportional hazard models to evaluate the adjusted association between tofacitinib and herpes zoster. They also analyzed incident cases HSV.  

Based on results, crude herpes zoster incidence associated with tofacitinib was 3.57/100 patient years. When tofacitinib use was compared to abatacept, through multivariable adjustments, researchers discovered herpes zoster risk was significantly elevated – HR 2.01 (95 percent CI 1.40 to 2.58).

RA biologics and abatacept rates, as well as adjusted HRs, were comparable. Older age, female sex, >7.5 mg/day of prednisone, prior outpatient infections, and a greater number of hospitalizations were also associated with herpes zoster risk.

The incidence rates for combined outcomes is greatest for tofacitinib (7.61/100 patient years). They are also significantly elevated after adjustment – HR=1.40, 95 percent CI 1.09 to 1.81).




Jeffrey R Curtis, Fenglong Xie, et. al. "Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis," Ann Rheum Dis doi:10.1136/annrheumdis-2016-209131

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