A Vaccine to Prevent Shingles—Treating Post-Herpetic Neuralgia in a Pre-Herpetic State
ABSTRACT & COMMENTARY
By Alan Z. Segal, MD
Assistant Professor, Department of Neurology, Weill Cornell Medical College, and Attending Neurologist at NewYork-Presbyterian Hospital
Dr. Segal is on the speaker’s bureau of Boehringer-Ingelheim.
Synopsis: There was an increased incidence of injection site reactions among vaccine treated patients, but no difference in the incidence of serious adverse events.
Source: Oxman MN, et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Eng J Med. 2005;352:2271-2284.
Herpes zoster, or shingles, occurs due to reactivation of Varicella-Zoster Virus (VZV) infection, which lies dormant in both cranial nerve and dorsal root ganglia. Shingles itself may be an annoyance, but the syndrome of post-herpetic neuralgia (PHN) is a source of severe and potentially debilitating chronic pain. Current treatment options, either topical (eg, lidocaine patches or capsaicin cream) or oral (eg, gabapentin, carbamazepine, or amitriptyline), are suboptimal. Shingles can occur at any age, but are more common in the elderly who tolerate medications poorly and are more likely than the young to develop PHN. VZV immunity, produced by infection as a child, wanes over time as cell-mediated immune responses become gradually less robust with age. Soon to enter middle age will be a population of patients who received a now available VZV-vaccine as a child. These individuals may have a lower shingles risk due to a lower latent viral ganglionic burden than those who had chicken pox as children. Alternatively, the childhood vaccine may produce an initially less robust immune response that would be even more prone to attrition over time, compared with that from natural disease. The study by Oxman and colleagues suggests that a booster zoster vaccine, given to healthy elderly volunteers, could effectively prevent shingles and significantly reduce post-herpetic pain complications.
Oxman et al’s study utilized the Oka/Merck VZV vaccine. This investigational agent contains approximately 18,700 to 60,000 plaque-forming units of live-attenuated virus. This is in contrast to the currently approved pediatric vaccine, which contains a lower inoculum of approximately 1350 units. The study included over 38,000 patients, aged greater than 60, who were randomized in double blind, randomized, placebo-controlled manner, and were followed for 3 years. There were 315 cases of shingles confirmed in vaccine treated patients, compared to 642 in the placebo group. Of note, the placebo incidence of shingles was approximately 1/100 person-years, exactly in keeping with known epidemiological data. There were 107 cases of post-herpetic neuralgia (27 in vaccine treated patients and 80 among placebo). This 66.5% reduction in post-herpetic neuralgia was highly statistically significant (P < 0.001). Overall efficacy was calculated according to a burden of illness score, which was 61.1% lower in vaccine treated patients (P < 0.001). There was an increased incidence of injection site reactions among vaccine treated patients, but no difference in the incidence of serious adverse events.
Commentary
Given the challenges that face neurologists in finding effective therapies for their patients with PHN, the potential to prevent this disease should come as welcome news. The high dose VZV vaccine used by Oxman et al is not yet available, and as Oxman et al note, it cannot be expected that their results could be replicated with the substitution of the low dose currently FDA-approved alternative. Widespread use of a VZV vaccine among the elderly would come at some expense, but it is likely that this would be outweighed by both the calculable costs of PHN treatments and the incalculable quality of life benefits that PHN prevention would bring. n
By Alan Z. Segal, MD Assistant Professor, Department of Neurology, Weill Cornell Medical College, and Attending Neurologist at NewYork-Presbyterian Hospital Dr. Segal is on the speakers bureau of Boehringer-Ingelheim. Synopsis: There was an increased incidence of injection site reactions among vaccine treated patients, but no difference in the incidence of serious adverse events.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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