SMALL INCREASE IN GBS WITH H1N1 VACCINATION 

A new report finds a "modest" increase in the risk for Guillain-Barré syndrome (GBS) among some 23 million Americans who received the influenza A (H1N1) monovalent vaccine as part of one of the "largest mass vaccination initiatives in recent US history."

Researchers found an excess of about 1.6 cases of GBS per million people vaccinated.

"In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks," the investigators, with lead author Daniel A. Salmon, PhD, from the National Vaccine Program Office, Office of the Assistant Secretary for Health, in the Department of Health and Human Services, Washington, DC, conclude.

Coauthor Bruce Gellin, MD, also from the National Vaccine Program Office in the Department of Health and Human Services, told Medscape Medical News that these findings quantify with some degree of precision the amount of excess risk for GBS occurring within the first 6 weeks after vaccination: that is, the risk in excess of the expected background rate.

"Vaccine safety is an important part of any immunization program," Dr. Gellin said. "Particularly given the magnitude of this program for the 2009 pandemic, there was, I think, a tremendous and maybe unprecedented cooperation among the various parts of government that run each of these different systems, so that we could put these data together and come up with the assessment we have."

Their report is published online March 13 in The Lancet. Funding for the surveillance projects was provided by the US federal government.

Previous Mass Immunization

GBS is a "rare but serious health condition in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death," the authors write.

Prior to the 2009 H1N1 vaccination campaign, the last national effort to vaccinate the US population was in 1976 against swine influenza, the researchers note in their paper. However, the initiative was later halted when an increased risk for GBS was recognized, with a relative risk of about 7 to 8, and when the expected pandemic didn't take place as expected. This increased relative risk associated with vaccination resulted in an estimated attributable risk of about 1 excess case per 100,000 vaccinations.

In 2004, the US Institute of Medicine (IOM) concluded that "the evidence favors acceptance of a causal relationship" between that 1976 influenza vaccine and GBS in adults. However, studies in the interim have had mixed results, the authors note. The most recent IOM report in 2011 concluded that the evidence is "inadequate to accept or reject" a causal relationship but noted that "an association cannot be confidently ruled out, particularly for future vaccine strains." (That review did not have the post-licensure safety available at that time for the 2009 H1N1 vaccines, Dr. Gellin points out.)

So in 2009, "commensurate with the size and scope," of the influenza A (H1N1) vaccination program, "the most comprehensive vaccine adverse event monitoring agenda in the USA to date was organized by the US Government," they write.

"The vaccine safety datalink (VSD), which is the USA's principal active surveillance system, was enhanced, several active surveillance systems that were at varying stages of growth were expanded rapidly (ie, databases from Medicare and the US Departments of Defense and Veterans Affairs), and new adverse event monitoring systems were developed specifically for monitoring of influenza A (H1N1) vaccination — ie, the emerging infections programme (EIP), and the post-licensure rapid immunization safety monitoring (PRISM) network."

The current paper, then, combines information from these 6 different adverse event monitoring systems into a meta-analysis including about 23 million vaccinated people. The primary analysis calculated incidence rate ratios and attributable risk of excess cases of GBS per million vaccinations, using a self-controlled risk-interval design.

A total of 77 GBS cases, meeting the Brighton Collaboration GBS case definition criteria level 1 and 2, were included in the primary analysis.

The researchers report that the influenza A (H1N1) monovalent vaccines used in the United States were associated with a "small" increased risk for GBS, with an incidence rate ratio of 2.35 (95% confidence interval, 1.42 - 4.01; P = .0003).

"Assuming a background rate of Guillain-Barré syndrome of about one case per 100 000 person-years, an incidence rate ratio of 2.35 translates into about 1.6 excess cases of Guillain-Barré syndrome per million people vaccinated," they note.

GBS vs Narcolepsy

Recently, reports from Europe suggest an increased risk for narcolepsy with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine, Pandemrix (GlaxoSmithKline).

Most recent among these is a study from England that showed a significant 14-fold increased risk for narcolepsy in children receiving the vaccination, pointing to a "causal association," with the vaccine, Elizabeth Miller, consultant epidemiologist, Health Protection Agency, Colindale, London, United Kingdom, and colleagues reported online February 26 in the BMJ.

Altogether, more than 30 million doses of Pandemrixwere administered in European countries during the H1N1 flu pandemic, but it was not used in the United States.

In August 2010, concerns were raised in Finland and Sweden about a possible association between narcolepsy and this vaccine. A 2012 study from Finland reported a 13-fold increased risk for narcolepsy in children and young people aged 4 to 19 years who got the vaccine. However, in October 2012, a review of the evidence by the European Medicines Agency's Committee on Human Medicinal Products concluded that evidence was not sufficient to confirm a link between the vaccine and narcolepsy cases.

Dr. Gellin points out that although they don't have information with which to look at attributable risk individually for each of the 5 or 6 vaccines used in the United States during the 2009 pandemic, they haven't seen any increased risk for narcolepsy or any other adverse events except GBS associated with the vaccines that were used in the United States. All the vaccines used were approved by the US Food and Drug Administration, and all were from manufacturers with experience producing seasonal influenza vaccines, he said.

Risks vs Benefits

Summing up, the researchers point out that they focused here only on the risk for GBS after vaccination with the influenza A (H1N1) vaccine, not the considerable benefits of vaccination.

"About 61 million cases of influenza A (H1N1) disease were reported in the USA during the 2009 pandemic, including about 274,000 H1N1-related admissions and about 12,470 deaths," they conclude. "H1N1 vaccines offered substantial protection against medically attended illness."

One recent study estimates the vaccination program prevented 700,000 to 1,500,000 clinical cases of influenza, 4000 to 10,000 hospital admissions, and more than 200 to 500 deaths, the authors note.

"Clinicians, policy makers, and those eligible for vaccination must consider the overall risks and benefits of vaccination, as defined by epidemiological studies, but should be assured that the benefits of influenza A (H1N1) 2009 monovalent inactivated vaccines greatly outweighed the risks."

The work was funded by the US federal government. The authors have disclosed no relevant financial relationships.

Lancet. Published online March 13, 2013. Abstract