Currently, the live zoster vaccine is recommended for all adults older than age 50 years. However, live vaccines are generally contraindicated for immunocompromised patients such as those with HIV, malignancy, or those receiving high-dose corticosteroids. The generally accepted recommendation for patients taking < 20 mg/d of prednisone for fewer than 14 days is that the zoster vaccine is safe, while patients taking higher doses or longer courses should wait until steroids have been stopped for a month. Cheetham and colleagues sought to further delineate the risks associated with administering the zoster vaccine to patients taking corticosteroids and other immunosuppressant drugs.
The study was conducted by using data derived from a vaccine safety database maintained by the CDC and several managed care organizations. Adults aged 18 years and older who received the zoster vaccine were included in the analysis. The types of immunosuppressant medications used by patients in the study included oral corticosteroids, non-biological disease-modifying antirheumatic drugs (DMARDs), and anti-rejection drugs. Those on immunosuppressant drugs were further characterized as current users, defined as having the drug dispensed between 30 days before and 5 days after vaccination, or remote users, defined as having the drug dispensed between 365 days and 30 days before vaccination. The primary outcomes measured were diagnosis of disseminated varicella zoster virus (VZV) of the central nervous system, lungs, or heart, and diagnosis of zoster within 1 to 42 days following vaccination.
Of 277,358 patients who received the zoster vaccine, 14,554 (5.2%) had an immunosuppressant drug dispensed between 365 days before and 5 days afterward. In the current users group, the median daily prednisone dose for low-dose corticosteroids (< 20 mg/d) was 17.5 mg and the duration was 8 days, while for the high-dose group (> 20 mg/d) the median dose was 35 mg and the duration was 28 days. During the 42-day window, no cases of disseminated VZV were identified in either the current or remote users groups. In the current user group, 25 cases of herpes zoster occurred, compared to 17 in the remote user group. The odds ratio for herpes zoster for the current vs. remote group was 2.97 (95% CI, 1.61-5.51).
COMMENTARY
Herpes zoster can be a very debilitating disease, and the introduction of an effective vaccine has been welcomed in the clinic. However, physicians are challenged to decide which patients should and should not be vaccinated, especially among those who are immunosuppressed. The evidence has been conflicting, with some studies showing an increased risk of developing zoster while on corticosteroids, while others reported no additional risk. Thus, the new study by Cheetham and colleagues is pragmatic because it provides further guidance about who should receive the zoster vaccine and when. The main finding of the study was the slightly increased risk of herpes zoster in the current users of immunosuppressant drugs for 42 days following zoster vaccination. The authors hypothesized that it was unlikely the herpes zoster experienced by the patients was caused by the vaccine strain due to the relatively short incubation period. In other words, it seems implausible that the Oka VZV strain could migrate to a dermatome and reemerge as a herpes zoster rash in only 42 days. A better explanation is that the herpes zoster was due to reactivation of latent zoster virus. Further research to test this hypothesis seems warranted.
There were a few limitations to the study. First, despite a large database of patients who received the zoster vaccine, the overall number of cases of herpes zoster in both the remote and current immunosuppressant drug groups was small (n = 42). Second, the investigators did not report whether any of the patients had their immunosuppressant drugs filled by pharmacies outside the database network, which would have led to bias toward the null hypothesis. Third, the investigators counted a drug being dispensed as a surrogate for the patient actually taking it, which might not always have been true. Finally, it is possible that some patients stopped their immunosuppressant drugs prior to zoster vaccination and did not inform their physician.
The take-home point from this study is that patients on immunosuppressive drugs (including low-dose corticosteroids) at the time of zoster vaccination seem to be at increased risk for herpes zoster. We now have evidence that these patients should be off their immunosuppressive drugs for at least four weeks prior to vaccination.
In adults >18 years, taking immunosuppressive medications at the time of zoster vaccination increased the risk for herpes zoster for up to 6 weeks afterward (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70).
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