Recombinant hepatitis B vaccine and the risk of multiple sclerosis: A prospective study
FrankDeStefano, Centers for Disease Control and Prevention, MS E61, 1600 Clifton Rd., Atlanta, GA 30333fxd1@cdc.gov
Eric S. Weintraub and Robert T. Chen
Submitted November 11, 2004
Hernan et al found a puzzling increased risk
of multiple sclerosis (MS) within three years of a hepatitis B
vaccination. [1] No previous epidemiological study has found a
significantly increased risk and a review by the U.S. Institute of
Medicine determined that the evidence favors rejection of a causal
association between hepatitis B vaccine and MS. [2]
We conducted one of the studies that did not find an increased risk. [3]. Differences between our study, which was conducted in three large
U.S. health maintenance organizations, and the GPRD study included: we
evaluated optic neuritis as well as MS; we included information from
personal interviews in addition to medical record data; and we
evaluated different time intervals. To determine if these differences
could account for the different findings, we reanalyzed our data using
similar methods as the GPRD study. [4]
In the re-analysis, we included
only MS cases (according to the International Panel criteria), assessed
relative risks by single years after vaccination, and further restricted
the analysis to documented data. When we restricted to
medical records data, we identified 119 eligible MS cases, of which only three
had been vaccinated. The odds ratios (ORs) were 0.4 (95% confidence
interval, 0.1 – 1.5) for ever versus never vaccinated, and 1.4 (0.1 -
23.6) for 0-1 year and 0.8 (0.1 - 8.9) for > 5 years after vaccination; in the intervening years ORs could not be estimated due to lack of vaccinated cases or controls.
When we
supplemented the medical record data with information from the
standardized personal interviews, we were able to include 276 cases of MS
in the analysis; the OR for ever versus never vaccinated was 0.8 (0.4 –
1.4). According to timing of vaccination, the ORs were 0.7 (0.3 - 2.0),
0.7 (0.2 - 2.5), and 0.6 (0.1 - 3.1), respectively, for 0-1, 1-2, and 2-3
years after vaccination. The main concern with the analysis that included
interview data is possible preferential recall of vaccinations by the
cases. That all the OR point estimates were <_1.0 argues="argues" against="against" this="this" possibility.="possibility." p="p"/> We found no increased risk of MS overall or at any time during
the first three years after hepatitis B vaccination. Restricting the
analysis to data from medical records did not alter this conclusion.
References
1. Hernan MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B
vaccine and the risk of multiple sclerosis: a prospective study. Neurology
2004;63:838-842.
2. Institute of Medicine. Hepatitis B vaccine and demyelinating
neurological disorders. In: Stratton K, Almario DA, McCormick MC, eds.
Immunization safety review. Washington, DC: The National Academies Press,
2002.
3. DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and
risk of central nervous system demyelinating diseases in adults. Arch
Neurol 2003;60:504–509.
4. DeStefano F, Weintraub ES, Chen RT. Detemining risk of multiple
sclerosis after hepatitis B vaccine: Time since vaccination and source of
data. Pharmacoepidemiol Drug Safety 2004;13:S143.
Hernan et al found a puzzling increased risk of multiple sclerosis (MS) within three years of a hepatitis B vaccination. [1] No previous epidemiological study has found a significantly increased risk and a review by the U.S. Institute of Medicine determined that the evidence favors rejection of a causal association between hepatitis B vaccine and MS. [2]
We conducted one of the studies that did not find an increased risk. [3]. Differences between our study, which was conducted in three large U.S. health maintenance organizations, and the GPRD study included: we evaluated optic neuritis as well as MS; we included information from personal interviews in addition to medical record data; and we evaluated different time intervals. To determine if these differences could account for the different findings, we reanalyzed our data using similar methods as the GPRD study. [4]
In the re-analysis, we included only MS cases (according to the International Panel criteria), assessed relative risks by single years after vaccination, and further restricted the analysis to documented data. When we restricted to medical records data, we identified 119 eligible MS cases, of which only three had been vaccinated. The odds ratios (ORs) were 0.4 (95% confidence interval, 0.1 – 1.5) for ever versus never vaccinated, and 1.4 (0.1 - 23.6) for 0-1 year and 0.8 (0.1 - 8.9) for > 5 years after vaccination; in the intervening years ORs could not be estimated due to lack of vaccinated cases or controls. When we supplemented the medical record data with information from the standardized personal interviews, we were able to include 276 cases of MS in the analysis; the OR for ever versus never vaccinated was 0.8 (0.4 – 1.4). According to timing of vaccination, the ORs were 0.7 (0.3 - 2.0), 0.7 (0.2 - 2.5), and 0.6 (0.1 - 3.1), respectively, for 0-1, 1-2, and 2-3 years after vaccination. The main concern with the analysis that included interview data is possible preferential recall of vaccinations by the cases. That all the OR point estimates were <_1.0 argues="argues" against="against" this="this" possibility.="possibility." p="p"/> We found no increased risk of MS overall or at any time during the first three years after hepatitis B vaccination. Restricting the analysis to data from medical records did not alter this conclusion.
References
1. Hernan MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004;63:838-842.
2. Institute of Medicine. Hepatitis B vaccine and demyelinating neurological disorders. In: Stratton K, Almario DA, McCormick MC, eds. Immunization safety review. Washington, DC: The National Academies Press, 2002.
3. DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003;60:504–509.
4. DeStefano F, Weintraub ES, Chen RT. Detemining risk of multiple sclerosis after hepatitis B vaccine: Time since vaccination and source of data. Pharmacoepidemiol Drug Safety 2004;13:S143.