Annette Langer-Gould1, Lei Qian2, Sara Y Tartof2, Sonu M Brara3, Steve J Jacobsen2, Brandon E Beaber3, Lina S Sy2, Chun Chao2, Rulin Hechter2, Hung Fu Tseng2. 1. Department of Research and Evaluation, Kaiser Permanente, Southern California, Pasadena2Department of Neurology, Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles. 2. Department of Research and Evaluation, Kaiser Permanente, Southern California, Pasadena. 3. Department of Neurology, Los Angeles Medical Center, Southern California Permanente Medical Group, Los Angeles.
Abstract
IMPORTANCE: Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE: To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES: Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES: All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS: We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE: We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.
IMPORTANCE: Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE: To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES: Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES: All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS: We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE: We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.
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