title: Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.
abstract: All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the most frequently discussed in association with A/H1N1 vaccination; reporting rates were generally within expected background rates.
authors.affiliation: European Medicines Agency, Pharmacovigilance and Risk Management Sector, Patient Health Protection Unit, London, United Kingdom.
authors.forename: Alina
authors.initials: A
authors.lastname: Isai
authors.forename: Julie
authors.initials: J
authors.lastname: Durand
authors.forename: Steven
authors.initials: S
authors.lastname: Le Meur
authors.forename: Ana
authors.initials: A
authors.lastname: Hidalgo-Simon
authors.forename: Xavier
authors.initials: X
authors.lastname: Kurz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D004673:Encephalomyelitis, Acute Disseminated / Q000139:chemically induced / Q000453:epidemiology; D020275:Guillain-Barre Syndrome / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines