Tofacitinib, Biologic DMARDs Associated with Higher Risk of Herpes Zoster in Patients with Rheumatoid Arthritis

Treatment with biologic disease-modifying antirheumatic drugs associated with a higher overall risk, incidence, and recurrence of herpes zoster for patients with rheumatoid arthritis.

Patients with seropositive rheumatoid arthritis (RA) treated with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) have a high risk for herpes zoster (HZ), according to a study published in Arthritis Research & Therapy.

Patients with rheumatic arthritis have a significantly increased risk of HZ. Previous research has suggested that there is a potential association between HZ and synthetic disease-modifying antirheumatic drugs (DMARDs), considered the standard of care for achieving sustained remission for patients with RA.

Researchers were particularly interested in the potential association between HZ and bDMARDs and tsDMARDs, which are also considered as treatment options for patients with RA who respond inadequately to traditional DMARDs. They conducted a study to explore the associations of first-line bDMARD with overall, incident, and recurrent HZ risks among patients with RA.

The study included 11,720 patients with seropositive RA who were prescribed a bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review and Assessment Service database. During a total of 34,702 person-years of follow-up, 1686 (14.4%) cases of HZ were observed, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs.

Patients with seropositive RA treated with first-line biologics or tofacitinib were found to be at high risk. Tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61–3.76; P < .001), incidence (aHR, 1.99; 95% CI, 1.18–3.37; P = .011), and recurrence (aHR, 1.99; 95% CI, 1.18–3.37; P = .011) of HZ, compared with that of the abatacept group.

The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatments with other bDMARDs. The association was significant even after controlling for potentially confounding factors, including age, glucocorticoid use, and comorbidities.

This finding aligned with previous research, according to the authors of the current study. Infliximab (aHR, 1.36; 95% CI, 1.06–1.74; P = .017) also increased overall HZ risk, as did adalimumab (aHR, 1.29; 95% CI, 1.02–1.64; P = .032).

History of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33–1.78; P < .001). The HZ risk among patients with RA and a history of HZ was about 1.5-fold higher than among patients with RA who had no history of HZ.

The findings demonstrated that HZ risk is significantly increased in patients with RA and a history of HZ after the initiation of bDMARDs or tsDMARDs, unlike that in the general population in which prior HZ may reduce the risk of occurrence.

Overall, the researchers determined that patients with seropositive RA treated with bDMARDs or tsDMARDs have a high HZ risk. The authors suggest that individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARDs for patients with RA, considering HZ risks.

The study authors identified some limitations in their research. The follow-up duration of the tofacitinib group was short due to active prescription after 2017, which may have caused bias in comparison with other bDMARDs. The researchers strictly limited the follow-up period to the first bDMARD drug survival, and HZ cases that occurred after drug failure or switching were not counted as events in the present study.

The HIRA database may not have captured all HZ cases. Additionally, no HZ vaccinations are available in South Korea, meaning that information regarding HZ vaccination was insufficient. The study authors encourage future research with additional clinical information to validate the independent association between bDMARD use and HZ risk.


Jeong S, Choi S, Park S M, Kim J, Ghang B, Lee E Y. Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study. Arthritis Res Ther. 2022;24.

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