Shingles Risks Similar for the RA Biologics

Published: Sep 10, 2014

By Nancy Walsh, Senior Staff Writer, MedPage Today

The risk of developing herpes zoster was similar among older patients with rheumatoid arthritis (RA) treated with the various different biologic agents, a retrospective study found.

The unadjusted incidence rate of cases of herpes zoster ranged from 1.61 per 100 patient-years for golimumab (Simponi) to 2.45 per 100 patient-years for certolizumab pegol (Cimzia), according to Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues.

After adjusting for multiple potential confounders such as age, sex, race, comorbidities, and use of other medications, there were no significant differences in hazard ratios for any of the biologics compared with the referent, which was abatacept (Orencia).

For instance, the hazard ratio for golimumab was 0.91 (95% CI 0.47-1.76), while the hazard ratio for certolizumab was 1.30 (95% CI 0.77-2.23), the researchers reported online in Arthritis Care and Research.

Although a live-attenuated vaccine for herpes zoster is available for individuals 50 and older, a million cases of shingles continue to occur annually in the U.S., with the vast majority being in patients who are older and immunocompromised from illness or the use of immune suppressing medications such as the biologics given for rheumatoid arthritis.

It's not been known whether differences in risk for herpes zoster exist for the various RA biologics, with their varying mechanisms of action, so Curtis and colleagues analyzed Medicare claims between 2006 and 2011 for new prescriptions for etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab, golimumab, tocilizumab (Actemra), rituximab (Rituxan), and abatacept.

Their analysis was limited to patients who were starting a new biologic after having previously used a different one.

"The requirement for prior treatment with a different biologic agent was implemented because some biologics are not typically used as first-line therapies, and patients with more refractory RA, having failed multiple biologics, might have different risks for herpes zoster," the researchers explained.

They found 29,129 new episodes of biologic treatment for RA in the Medicare database for the specified time period, and 423 cases of herpes zoster during follow-up, which ended when patients stopped that specific biologic, switched to another, developed excluded conditions such as cancer, died, had the shingles diagnosis, or until the end of the study in 2011.

A total of 28.8% of the new treatment exposures were for abatacept, which is a T-cell co-stimulation modulator, while 14.8% were for rituximab, a B-cell depleting agent, and 6.1% were for tocilizumab, an interleukin-6 receptor blocker.

Among the tumor necrosis factor inhibitors, 15.4% were for adalimumab, 12.4% were for infliximab, 12.2% for etanercept, 5.8% for certolizumab, and 4.4% for golimumab.

Patients who developed shingles were older (67 versus 64), had used glucocorticoids during the previous year, and were less likely to be disabled or on Medicaid.

As with golimumab and certolizumab, adjusted hazard ratios for the development of herpes zoster for the different biologics were nonsignificant:

• Adalimumab, 1.04 (95% CI 0.72-1.51)
• Etanercept, 1.26 (95% CI 0.87-1.81)
• Infliximab, 0.98 (95% CI 0.69-1.39)
• Rituximab, 1.20 (95% CI 0.88-1.63)
• Tocilizumab, 1.05 (95% CI 0.60-1.84)

In contrast, patients who used glucocorticoids did have higher risks. For those on doses above 7.5 mg per day, the hazard ratio was 2.35 (95% CI 1.81-3.04), and for those on lower doses the hazard ratio was 1.55 (95% CI 1.25-1.94).

Patients who had received the shingles vaccine before initiating the biologic had lower risks (HR 0.79, 95% CI 0.39-1.61), but rates of vaccination were very low, at 0.4% in 2007 and 4.1% in 2011.

These low rates "indicate a compelling need for vaccination for RA patients," Curtis and colleagues observed.

"However, this may present practical challenges for patients to follow guidance to discontinue all biologics, allow for a washout, vaccinate, wait 4 additional weeks, and then initiate a new biologic," they noted.

Nonetheless, the lack of vaccine usage suggests "a need for greater awareness among rheumatologists to provide this important preventive health service," the authors concluded.

Limitations of the study included the lack of information on severity of disease and potential confounding lifestyle factors.