A Multicenter Case-Control Prospective Study to Assess the Risk of Immune Thrombocytopenia (ITP) Associated with Vaccines in Adults Using the PGRx-ITP Registry

Immune thrombocytopenia (ITP) is thought to result from an autoimmune mechanism, and some case-reports have suggested that immunizations could be involved and trigger the autoimmune process. This prospective multicenter case-control study investigated for the first time associations between ITP and vaccination in adults, particularly between ITP and influenza vaccinations.

Over a three year period, a network of 15 physicians from hematology and internal medicine referral centers across France recruited newly diagnosed cases of primary ITP in patients aged over 15 years fulfilling the ITP standardized criteria of the American Society of Hematology. Recruiting physicians completed standardized forms for each patient and every patient underwent a standardized 1 hour-interview focused on previous medications and vaccinations in the last 12 months. Incident ITP cases were compared to sex and age-matched controls selected and recruited from general practice settings, also from the same geographically areas of France. The method of referent recruitment has been described elsewhere (Grimaldi-Bensouda et al. 2010 Pharmacoepidemiol Drug Saf 2010;19(6):591–5). Controls were also interviewed in the same standardized way as cases. Cases and control were compared in respect of various descriptive factors and potential risk factors for ITP. Written or other confirmation of vaccinations was sought from both the patient and his/her physician. The time window defining exposure to vaccines was 12 months before the index date. In secondary analysis, the most prevalent vaccines in adults were analyzed.

Two hundred and twenty four cases fulfilling the inclusion criteria and 4412 were included in the study. Seventy eight of the 224 cases (34.8%) and 1566 of 4412 controls (35.5%) received a vaccination within this time window [adjusted odds ratio 0.97, 95% confidence interval 0.70–1.33]. Twenty percent of the cases and 26% of controls received an influenza vaccine [adjusted odds ratio 0.66, 95% confidence interval 0.45–0.98]. Other prevalent vaccines in adult are currently under study.

This systematic case-control design is well-suited to study rare disorders such as ITP and few such studies have been conducted. Another advantage was the minimization of recall bias because questions about vaccinations were included in a standardized interview focusing on exposure to all medications. When all vaccines were considered, we found no association between vaccination and the incidence of ITP in either crude or adjusted analyses. Moreover, cases were less likely than controls to have been vaccinated against influenza in the 12 months before the index date.

Grimaldi-Bensouda:LA-SER: Employment; INSERM: I was the recipient of a research fellowship from the INSERM (French National Institute for Health and Medical Research) at the time of the study. Leighton:LA-SER Europe Ltd: Employment. Aubrun:LA-SER Europe Ltd: Employment. Abenhaim:LA-SER Europe Ltd: I'm a stock owner and chairman of LA-SER, the company conducting the study.