Advice for Consideration of Quadrivalent (A, C, Y, W135) Meningococcal Conjugate Vaccine, for use by Provinces and Territories

Summary

In 2006, the first quadrivalent meningococcal conjugate vaccine (Menactra™) was authorized for use in Canada. This statement provides the evidence based analysis needed for consideration of this vaccine for immunization program planning by provinces and territories. Provinces and territories are responsible for the delivery of immunization programs and will consider their own circumstances in making decisions about the vaccine based on the critical analysis provided in this report.

Historically, the epidemiology of meningococcal disease in Canada has been characterized by an endemic background and occurrence of large epidemics and smaller outbreaks at irregular intervals. There are marked differences between serogroups, serogroup B strains causing the majority of sporadic cases and virulent serogroup C clones causing most of the outbreaks observed during the last two decades. To date, it has not been possible to reliably predict the epidemiology of meningococcal disease, therefore the occurrence of new epidemics or outbreaks caused by virulent clones of any serotype cannot be excluded in Canada.

In all existing trials in persons aged 2 years or more, the short-term immunologic response to Menactra™ was non-inferior to the response to the quadrivalent polysaccharide vaccine. Menactra™ generated antibodies having better functional characteristics and longer persistence, while inducing a strong anamnestic response following a booster dose without hyporesponsiveness. Thus, Menactra™ should be preferred to the quadrivalent polysaccharide vaccine for all indications of a quadrivalent or a serogroup A, Y or W135 meningococcal vaccine those aged 2 years and older. The field effectiveness of monovalent serogroup C conjugate vaccines has been evaluated in large post-marketing epidemiological studies. Currently, there are no data on the clinical effectiveness of Menactra™. There has been no immunologic study providing a head-to-head comparison of Menactra™ with field tested serogroup C conjugate vaccines containing either the CRM₁₉₇ carrier protein derived from the diphtheria toxoid (Meningitec™, and Menjugate™) or the tetanus toxoid (Neis Vac-C™). Although the immune response of Menactra™ was compared to the response of the polysaccharide vaccine, and was non-inferior for serogroup C, it is established that the polysaccharide vaccine provides a low level of protection of short duration for this serogroup in children. For these reasons, until the results of new studies are available, monovalent serogroup C conjugate vaccines should be preferred for all indications of vaccination against serogroup C meningococcal disease, especially for children. While the effectiveness of polysaccharide vaccines to prevent serogroup A and C IMD has been demonstrated in experimental and observational studies in adolescents and adults, immunologic studies have shown that Menactra™ (Men4-DT) is a more potent vaccine. For this reason, Men4-DT could be considered for routine immunization of adolescents, including those already immunized with a monovalent serogroup C conjugate vaccine at a young age.

The experience of administration of Menactra™ in nine clinical trials involving more than 10 000 subjects is very reassuring and adverse events were not substantially different than those reported in the control groups vaccinated with a quadrivalent polysaccharide vaccine. In the US, Menactra™ is widely used for vaccinating adolescents and college students. As of February 25, 2008, more than 15 million doses of Menactra™ have been distributed, and the Vaccine Adverse Event Reporting Systems (VAERS) has received 26 confirmed case reports of GBS within 6 weeks of receipt of Menactra™ meningococcal vaccination. A causal relationship has not been established, but the existence of a risk of very small magnitude cannot be excluded.

The preferred indication for Menactra™ in Canada is for vaccination of adolescents at the age of 12 years, just before the increase in incidence meningococcal disease that occurs at the age of 13 years. For adolescents not previously vaccinated, this would be a primary vaccination, and for those previously vaccinated with a monovalent serogroup C conjugate vaccine at a young age, this would be a booster dose for serogroup C and a primary vaccination for serogroups A, Y and W135. Vaccination of an important proportion of adolescents could significantly reduce transmission of pathogenic strains in the entire population, as the prevalence of carriage of N. meningitidis is maximal in this age group.

Using a vaccine purchase price of $70 per Menactra™ dose, annual program costs for adolescents would range between $19 and $29 million in Canada. A simulation model was developed for assessing both the direct and indirect effects of a booster dose at 12 years of age with either a monovalent C or a quadrivalent ACYW135 meningococcal conjugate vaccine in a cohort of Canadians immunized at 12 months with a monovalent C conjugate vaccine ($23 per dose). Revaccination at 12 years using the serogroup C vaccine would reduce the burden of disease by 55% at no marginal cost (a minor saving is predicted). Using Menactra™ for the booster dose would result in a disease reduction of 78% for a marginal cost of $31 000 per QALY gained compared to one dose of serogroup C vaccine at 12 months. Comparing Menactra™ with serogroup C vaccine as a booster dose, the incremental cost-effectiveness ratio would be $113 000 per QALY.

Meningococcal disease is amongst the most feared conditions, and the inclusion of a new vaccine in the regular immunization schedule of adolescents would be well received by the majority of the population and health care professionals.

Ideally, meningococcal vaccination during adolescence should be performed at 12 years of age, via a school-based program (Grade 7) and combined with other vaccinations. The decision to use Menactra™ or a monovalent serogroup C product is an issue of provincial/territorial priorities in resource allocation.

List of abbreviations

IMD: invasive meningococcal disease

Men4-DT: quadrivalent (serogroup A, C, W135 and Y) polysaccharide diphtheria toxoid protein conjugate meningococcal vaccine (Menactra™)

MenC-C: monovalent serogroup C meningococcal conjugate vaccine