title: Post-marketing monitoring of intussusception after rotavirus vaccination in Japan.
abstract: OBJECTIVE
  Rotarix(TM) was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that Rotarix(TM) may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and Rotarix(TM) vaccination in Japan.
  
  
  METHODS
  All IS cases spontaneously reported post-vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post-vaccination) and for each vaccine dose (two doses).
  
  
  RESULTS
  Before January 2013, approximately 601 000 Rotarix(TM) doses were distributed in Japan. For a risk period of 7 days post-dose 1 and post-dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed-to-expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post-dose 1 and post-dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed-to-expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively.
  
  
  CONCLUSIONS
  A statistically significant excess of IS cases was observed within 7 days post-dose 1, but not post-dose 2. These results are consistent with previous observations in large post-marketing safety studies in other world regions.
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bauchau
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Lionel
authors.identifier: http://orcid.org/0000-0001-7354-6475
authors.initials: L
authors.lastname: Van Holle
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Olivia
authors.initials: O
authors.lastname: Mahaux
authors.affiliation: Health Economics Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Holl
authors.affiliation: Japan Vaccine Co., Ltd., Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Hubert
authors.initials: H
authors.lastname: Buyse
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D015994:Incidence; D007443:Intussusception / Q000139:chemically induced / Q000453:epidemiology*; D007564:Japan / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data; D018570:Risk Assessment; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: Japan; RotarixTM; human rotavirus vaccine; intussusception; pharmacoepidemiology; post-marketing surveillance