Observational safety study of specific outcomes after trivalent cell culture seasonal influenza vaccination (Optaflu®) among adults in THIN database of electronic UK primary healthcare records

Purpose

To investigate the safety of trivalent seasonal influenza vaccine (TIVc) (Optaflu^®), the first cell culture seasonal trivalent influenza vaccine available in Europe.

Methods

Codes and unstructured text in adult electronic healthcare records (The Health Improvement Network) were searched for a TIVc brand name or batch number and possible outcomes within a 3 month pre‐ to 6 month post‐TIVc exposure study period (2012‐2015). The outcomes were severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis (optic and brachial), vasculitis, inflammatory bowel disease, and thrombocytopenia. Risk periods were defined based on biologically plausible time frame postvaccination when an outcome caused by the vaccine might be expected to occur. Possible outcomes were adjudicated against outcome specific case definitions and a date of onset assigned by using electronic and other medical records. Observed (risk period) to expected (outside risk and preexposure periods) rate ratios, postexposure incidence, and plots of time from exposure to outcome were reported.

Results

Sixteen of 1011 events from 4578 exposures fulfilled a primary case definition and had a date of onset during the study period. Three were in observed time. The observed‐to‐expected rate ratios were (3.3, 95% CI 0.3, 31.7) for convulsions and (1.5, 95% CI 0.2, 14.9) for thrombocytopenia with 1 outcome each in observed time. There was 1 incident inflammatory bowel disease in observed, but none in expected, time.

Conclusion

The small sample size restricts interpretation; however, no hypothesis of an increased risk of a study outcome was generated. Adjudication of events against case definitions to reduce misclassification of onset and outcomes allowed use of precise risk periods. KEY POINTS

• This observational study did not generate a hypothesis of an association between the first cell‐culture seasonal influenza vaccination available in the European Union and any of the study outcomes (severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis [optic and brachial], vasculitis, inflammatory bowel disease [IBD], and thrombocytopenia). The small sample size limits interpretation of the results.
• The review of each possible outcome identified from electronic healthcare records against case definitions was included to minimize misclassification of time and outcomes and allow the use of precise risk‐periods in an observed‐to‐expected within cohort analysis. Plots of time from exposure to outcome were included to assess the risk windows.

     

Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study

Background: Little is known about the use of acid-suppressing treatments and related safety events in children.

Objective: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time.

Methods: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H₂RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up.

Results: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H₂RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n?=?36; 39.1%). In the H₂RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n?=?62; 32.1%). The incidence of most safety outcomes was higher in the H₂RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI)?=?2.25–4.28] vs 0.49 per 1,000 person-years [95% CI?=?0.22–1.07]) and gastroenteritis (5.27 [95% CI?=?4.11–6.75] vs 3.04 per 1,000 person-years [95% CI?=?2.20–4.20]).

Conclusion: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H₂RAs. Overall, more safety outcomes occurred in the H₂RAs cohort than in the PPI cohorts.