No Risk of MS Found in GlaxoSmithKline Vaccine for Swine Flu, Canadian Study Says

Protecting the public against an outbreak like the swine flu using GlaxoSmithKline‘s vaccine Arepanrix — or a similar vaccine with an AS03 adjuvant delivery system — does not increase a risk of multiple sclerosis (MS), a population study conducted in Canada reports.

The study, “Registry Cohort Study to Determine Risk for Multiple Sclerosis after Vaccination for Pandemic Influenza A(H1N1) with Arepanrix, Manitoba, Canada,” was published in the journal Emerging Infectious Diseases.

A worldwide breakout (called a pandemic) of swine flu — caused by infection with H1N1 virus — occurred in 2009. Soon afterward, researchers noticed an increase in MS incidence among residents of three Swedish counties treated with Pandemrix, a vaccine against infection by the H1N1 virus. The vaccine is composed by inactivated virus proteins combined with the adjuvant system AS03, a combination of α-tocopherol (a type of vitamin E) and squalene (a natural substance found in olive oil) in an oil-in-water emulsion.

Another Swedish study suggested the vaccine was linked to a greater risk of sensory nerve cells response damage (paraesthesias), but not multiple sclerosis.

Although alarming, these studies were not designed to specifically evaluate a potential association between the vaccine and MS risk, and their conclusions were controversial.

Because the AS03 adjuvant is a prime delivery system for such vaccines, concerns about its safety and possible connection to diseases like MS remained.  The European Medicine Agency, specifically, requested a study evaluating use of the AS03-adjuvant in vaccines and MS risk.

A Canadian research team responded by looking at MS incidence among residents of Manitoba, comparing those who were vaccinated with Arepanrix, also an AS03-adjuvanted H1N1 vaccine, and those who were not. [MS rates are high in Canada due to a complex interplay of genetic and environmental factors, and particularly high in central and western provinces such as Manitoba.]

Using a database study (NCT02367222), the researchers reviewed the clinical records of hospitalization, physician utilization, vaccination, and prescriptions for the province’s entire population.

Between September 2009 and March 2010, a total of 341,347 people received at least one dose of influenza A (H1N1) vaccine, while 485,941 other — matched for age and sex — were unvaccinated. Among those vaccinated, 57% were given Arepanrix, 30% received a standard influenza vaccine, and 13% received both.

At one year follow-up, 106 cases of MS were reported among people not given an influenza vaccine, compared to 69 cases among those who were vaccinated. The age-adjusted incidence rate of MS was 17.7 cases per 100,000 person-years in the Arepanrix group, and 24.2 per 100,000 in the unvaccinated group.

Researchers also found a higher MS incidence rate among those given a standard influenza vaccine compared to those treated with Arepanrix.

The team also looked at whether Arepanrix vaccination might be linked to a higher risk of any other disease characterized by nerve cell damage. These analyses again failed to produce any meaningful association between disease incidence and influenza vaccination.

Similar patterns of MS incidence were found when the researchers extended the analysis for a median follow-up of three years.

“The AS03 adjuvant, a candidate for inclusion in future pandemic vaccines, does not appear to increase the short-term risk for MS when included in influenza vaccines,” the study concluded.

Despite the sample large size, researchers highlighted that these findings may not reproduce those of other populations, because of differences in geographic location, ethnic composition, and access to the pandemic vaccines. Associated risks may also change if a future pandemic is due to another virus.

Still, findings regarding the “safety of the AS03 adjuvant are likely to hold true” for future vaccines, the researchers added.