Autoimmune Conditions Following Human Papillomavirus Vaccine
Autoimmune Conditions Following Human Papillomavirus Vaccine
Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K-L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.
Objective. An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.
Design. Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.
Setting. Two managed care organizations in California.
Subjects. Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008.
Outcome. Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).
Results. Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR = 1.29, 95% confidence interval: 1.08–1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.
Conclusions. No autoimmune safety signal was found in women vaccinated with HPV4.
Vaccination with the quadrivalent human papillomavirus (HPV) vaccine, HPV4, presents an opportunity to reduce the burden of cervical cancer and other conditions caused by HPV types 6, 11, 16 and 18. HPV4 demonstrated high efficacy in preventing clinical outcomes associated with new infection of HPV vaccine types. The antigen presented in HPV4 is the L1 major capsid proteins of the four HPV vaccine types. HPV4 uses aluminium-containing adjuvant but does not contain thimerosal or antibiotics. In June 2006, HPV4 was approved by the US Food and Drug Administration (FDA) as a regimen of three injections given over 6 months to women between the ages of 9 and 26 years. The Advisory Committee on Immunization Practices subsequently recommended routine HPV4 vaccination for girls who are 11–12 years old.
Between 2006 and 2010, a safety surveillance study of HPV4 in routine use amongst women was conducted as a postlicensure commitment to the FDA, the European Medicines Agency and other regulatory authorities. This study was conducted in collaboration between two managed care organizations, Kaiser Permanente Southern California (KPSC) and Kaiser Permanente Northern California (KPNC), as a retrospective analysis of information from medical records and other databases. The study objectives were to monitor (i) general safety, (ii) pregnancy outcomes, and (iii) new onset of autoimmune conditions following HPV4 vaccination. Autoimmune reactions have been a long-standing concern surrounding vaccination. However, most speculated associations have stemmed from case reports lacking confirmation by large, controlled epidemiologic studies. Thus, well-designed postlicensure safety studies for newly approved vaccines facilitate proper evaluation of their autoimmune safety. This report presents findings from the autoimmune surveillance component of the postlicensure safety study of HPV4 in women.
Abstract and Introduction
Abstract
Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K-L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.
Objective. An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.
Design. Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.
Setting. Two managed care organizations in California.
Subjects. Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008.
Outcome. Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).
Results. Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR = 1.29, 95% confidence interval: 1.08–1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.
Conclusions. No autoimmune safety signal was found in women vaccinated with HPV4.
Introduction
Vaccination with the quadrivalent human papillomavirus (HPV) vaccine, HPV4, presents an opportunity to reduce the burden of cervical cancer and other conditions caused by HPV types 6, 11, 16 and 18. HPV4 demonstrated high efficacy in preventing clinical outcomes associated with new infection of HPV vaccine types. The antigen presented in HPV4 is the L1 major capsid proteins of the four HPV vaccine types. HPV4 uses aluminium-containing adjuvant but does not contain thimerosal or antibiotics. In June 2006, HPV4 was approved by the US Food and Drug Administration (FDA) as a regimen of three injections given over 6 months to women between the ages of 9 and 26 years. The Advisory Committee on Immunization Practices subsequently recommended routine HPV4 vaccination for girls who are 11–12 years old.
Between 2006 and 2010, a safety surveillance study of HPV4 in routine use amongst women was conducted as a postlicensure commitment to the FDA, the European Medicines Agency and other regulatory authorities. This study was conducted in collaboration between two managed care organizations, Kaiser Permanente Southern California (KPSC) and Kaiser Permanente Northern California (KPNC), as a retrospective analysis of information from medical records and other databases. The study objectives were to monitor (i) general safety, (ii) pregnancy outcomes, and (iii) new onset of autoimmune conditions following HPV4 vaccination. Autoimmune reactions have been a long-standing concern surrounding vaccination. However, most speculated associations have stemmed from case reports lacking confirmation by large, controlled epidemiologic studies. Thus, well-designed postlicensure safety studies for newly approved vaccines facilitate proper evaluation of their autoimmune safety. This report presents findings from the autoimmune surveillance component of the postlicensure safety study of HPV4 in women.
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