Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

8th Canadian Immunization Conference

Toronto, Ontario / November 30-December 3, 2008

As reported here by Dr. Vivien Brown, Department of Family and Community Medicine, University of Toronto, Ontario, the herpes zoster (HZ) vaccine would become standard of care for adults <u>></u>60 years of age, according to recent guidelines from the Canadian Medical Protection Association (CMPA). Physicians would need to educate patients about the vaccine and its ability to reduce the incidence of HZ and post-herpetic neuralgia (PHN). The CMPA also reminded physicians that they would need to document their discussion with patients, along with reasons given by patients if they refuse the vaccine. “The CMPA says that we must be prepared to provide information about vaccination for patients,” Dr. Brown confirmed. Patients have the right to refuse, the CMPA also pointed out, “but if they do not know about the vaccine, then they cannot make an informed decision,” she added.

Growing Incidence, Unsatisfactory Pain Control

It is important for patients to be aware that approximately 95% of Canadians have been infected with the varicella zoster virus by the time they are young adults. Each year, approximately 130,000 cases of HZ occur in Canada as the virus becomes reactivated and travels to the skin and the spinal cord to produce its characteristic rash and acute neuropathic pain. The incidence of HZ is also increasing, as Dr. Peter Watson, Assistant Professor of Medicine, University of Toronto, reminded delegates, a reflection of the aging population and a growing number of patients who are immunosuppressed. Fifteen per cent of HZ episodes will result in PHN, but this percentage approximately doubles in patients over the age of 65, Dr. Watson noted. In patients whose PHN persists for a year, 50% will continue to suffer from it, he added. The pain of acute zoster is difficult to control and aggressive treatment of HZ with antivirals only modestly reduces the acute pain. Antiviral therapy also needs to be started within 72 hours of symptom onset and it is often difficult to diagnose acute zoster within that window of time, as rash onset is often delayed, Dr. Watson explained.

Furthermore, even when acute zoster is correctly diagnosed and treated, between 30% and 35% of patients still have persistent pain and approximately one-half of those who go on to develop PHN experience either intractable or unsatisfactorily-controlled pain despite the use of antidepressants, anticonvulsants and opioids. As Dr. Watson indicated, various trials in which the tricyclic antidepressants have been evaluated indicate that anywhere from about one- to two-thirds of patients with PHN have either no response to treatment or a poor response. Findings from the MASTER study presented here by Drolet et al. also indicate that the burden of illness (BOI) from acute zoster as well as PHN is highly significant.

Defining the BOI for a patient with acute zoster as the area under the curve of worst pain over time until cessation of pain, researchers found that the average HZ BOI in a group of 277 incident cases was 211 and that it increased with age, from 170 in patients between the ages of 50 to 59 years up to 250 in those >70 years of age. Among patients who went on to develop PHN, the HZ BOI was 455, a reflection of both the greater severity of pain during the first 90 days after rash onset, the severity of the acute rash and a painful prodrome, all known risk factors for PHN.

Dr. Watson concluded that HZ is a common cause of nerve injury pain and PHN is its most common and feared complication. “For me, after treating these conditions for 25 years or more, vaccination against zoster appears to be critical,” he added.

Shingles Prevention Study

Like most adult vaccines, the HZ vaccine does not prevent all episodes of acute zoster but it does attenuate the severity of an episode and prevents a substantial proportion of PHN. As discussed by Dr. Caroline Quach, Assistant Professor of Pediatrics, McGill University, Montreal, Quebec, the SPS (Shingles Prevention Study) involving approximately 38,000 participants showed that at a mean follow-up of 3.1 years, a single dose of the vaccine reduced the incidence of HZ by approximately 50% and that of PHN by approximately 66% compared with placebo.

The vaccine also reduced the BOI score (a measure that included both the severity and duration of pain from HZ and PHN) by 61.1% relative to placebo. A recent update of the SPS study cited by Dr. Quach also demonstrated that the cumulative efficacy of the vaccine was still about 40% against HZ and approximately 58% against PHN during a follow-up from study end point to seven years. For the BOI score, the vaccine remained fairly constant over the same seven-year follow-up with a reduction in the BOI score at approximately 60% relative to placebo.

Reanalysis of safety data in a subgroup of the SPS cohort also demonstrated that local adverse events (AEs), including erythema, swelling and pain, were more frequent among vaccine recipients and in younger patients. However, the incidence of serious AEs at 1.4% was identical in both groups, “which was comforting,” Dr. Quach noted. A handful of SPS participants were also naive to varicella at the time of vaccination and even in this group, the vaccine was equally effective and was not associated with an excess risk of AEs, she added.

A meta-analysis also indicated that the HZ vaccine is at least as or more efficacious in adults between the ages of 50 and 59 years. Out of a total of 1122 recipients <u>></u>50 years of age, the geometric mean titre (GMT)-fold increase was 2.3 following vaccination over baseline vs. 2.3-fold higher in recipients <u>></u>60 years of age. Studies comparing the freezer vs. the fridge-stable vaccine formulations also indicate that the efficacy is comparable between the two, Dr. Quach reported. (The freezer-stable formulation is expected to be available some time this year in Canada.)

Practical Considerations

“HZ is a relatively benign disease in younger patients but it is quite morbid in the elderly and considering we have no other means of preventing PHN, you should vaccinate patients between the ages of 60 to 69 years when the vaccine is much more immunogenic rather than wait until they are older,” Dr. Quach indicated. She cautioned, however, that the HZ vaccine should not be given concomitantly with the 23-valent pneumococcal vaccine as the pneumococcal vaccine (although not the influenza vaccine) attenuates response to the HZ vaccine.

Recommendations from the Advisory Committee on Immunization Practices indicate that patients with a history of HZ can still be vaccinated. If immunosuppression is anticipated, patients may receive one dose of the HZ vaccine <u>></u>14 days prior to immunosuppression, while antivirals should be stopped 24 hours before until 14 days after vaccination if patients are on chronic antiviral therapy.

Related sessions of interest at this meeting:

“Zoster and Post-Herpetic Neuralgia: Is This a Disease Worth Preventing? A Burning Question.” Chair: V Brown.

O13. “Quality-of-life-years (QALY) lost during the first 90 days after onset of herpes zoster (HZ).” M Drolet.

P78. “The pain burden in the first 90 days after the onset of HZ.” M Drolet, RW Johnson, MJ Levin, MN Oxman, DM Patrick, KE Schmader, JA Mansi.