Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood
MichelLievre, Lyon 1 University
Members of the Epidemiology working group of the French pharmacovigilance commission: Dominique Costagliola, Stephen Evans, Annie Fourrier, Jean-Louis Imbs, Daniel Levy-Bruhl, Louis Merle, Joelle Micallef, Emmanuel Oger
Published March 10, 2009
In a new analysis of a case-control study based on the French KIDSEP cohort, Mikaeloff et al. conclude that there is no overall association of
hepatitis B vaccine (HB) with acute onset demyelinating disease but that there is a long-term increase in the risk of multiple sclerosis (MS) in
children compliant with national vaccination schedules and immunized
against HB with the Engerix B® vaccine. [1]
Unfortunately, these results
were leaked to the lay press before their publication in Neurology®,
fueling new rumors about the risk of HB vaccination. We would like to
stress major interpretational issues that preclude any reliable
conclusion from being drawn about a possible link in this study, between
the Engerix R® vaccine, and the risk of MS in children.
A very large number of analyses were undertaken. A total of 50 results
appear in the article, and the list of “sensitivity” analyses suggests
that many more were done. The probability of detecting several
significant associations through pure chance was therefore very high.
Concluding that there is a difference between Engerix B® and other
vaccines because the odds ratio for MS is significant for Engerix B® and
non-significant for the other vaccines results from an error in
interpretation. The confidence intervals of the odds ratios for
the various vaccines largely overlap, and a significant interaction
between the risk of MS and vaccine brand cannot therefore be demonstrated.
Restricting the investigation to children compliant with the French
vaccine recommendations was based on the assumption of a possible bias in
the responses of the controls in favor of the best vaccinated children.
However, the very existence of such a bias should have been questioned by
the investigators when confronted with similar levels of compliance in
cases and controls.
The sub-group analysis results in a considerable reduction in sample
size, with a loss of more than 50% of cases. The role played by the delay between vaccination and MS is not clear.
In the sub-analysis of “compliant” children, the odds ratio is 0.45 (IC
95% = [0.12 – 1.71]) for a 1-2 year delay, and moves to 2.12 (IC 95% =
[1.00 – 4.48]) for a >3 year delay.
In conclusion, the benefit/risk balance of vaccination with any
vaccine against HB in children should not be called into question on
the basis of sub-group results in this study.
Reference
1. Mikaeloff Y, MD, Caridade G, Suissa S, Tardieu M. Hepatitis B
vaccine and the risk of CNS inflammatory demyelination in childhood. Neurology 2009;72:873-880.
Disclosure: The authors report no disclosures.
The authors and the editorialists were offered the opportunity to respond but declined.
In a new analysis of a case-control study based on the French KIDSEP cohort, Mikaeloff et al. conclude that there is no overall association of hepatitis B vaccine (HB) with acute onset demyelinating disease but that there is a long-term increase in the risk of multiple sclerosis (MS) in children compliant with national vaccination schedules and immunized against HB with the Engerix B® vaccine. [1]
Unfortunately, these results were leaked to the lay press before their publication in Neurology®, fueling new rumors about the risk of HB vaccination. We would like to stress major interpretational issues that preclude any reliable conclusion from being drawn about a possible link in this study, between the Engerix R® vaccine, and the risk of MS in children.
A very large number of analyses were undertaken. A total of 50 results appear in the article, and the list of “sensitivity” analyses suggests that many more were done. The probability of detecting several significant associations through pure chance was therefore very high.
Concluding that there is a difference between Engerix B® and other vaccines because the odds ratio for MS is significant for Engerix B® and non-significant for the other vaccines results from an error in interpretation. The confidence intervals of the odds ratios for the various vaccines largely overlap, and a significant interaction between the risk of MS and vaccine brand cannot therefore be demonstrated.
Restricting the investigation to children compliant with the French vaccine recommendations was based on the assumption of a possible bias in the responses of the controls in favor of the best vaccinated children. However, the very existence of such a bias should have been questioned by the investigators when confronted with similar levels of compliance in cases and controls.
The sub-group analysis results in a considerable reduction in sample size, with a loss of more than 50% of cases. The role played by the delay between vaccination and MS is not clear. In the sub-analysis of “compliant” children, the odds ratio is 0.45 (IC 95% = [0.12 – 1.71]) for a 1-2 year delay, and moves to 2.12 (IC 95% = [1.00 – 4.48]) for a >3 year delay.
In conclusion, the benefit/risk balance of vaccination with any vaccine against HB in children should not be called into question on the basis of sub-group results in this study.
Reference
1. Mikaeloff Y, MD, Caridade G, Suissa S, Tardieu M. Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood. Neurology 2009;72:873-880.
Disclosure: The authors report no disclosures.
The authors and the editorialists were offered the opportunity to respond but declined.