Effects of high‐dose versus standard‐dose quadrivalent influenza vaccine among patients with diabetes: A post‐hoc analysis of the DANFLU‐1 trial

Abstract

AbstractAimHigh‐dose quadrivalent influenza vaccine (QIV‐HD) has been shown to be more effective than standard‐dose (QIV‐SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all‐cause hospitalizations (first + recurrent), and a composite of all‐cause mortality and hospitalization for pneumonia or influenza.MethodsDANFLU‐1 was a pragmatic, open‐label trial randomizing adults (65‐79 years) 1:1 to QIV‐HD or QIV‐SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all‐cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c.ResultsOf the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV‐HD, compared with QIV‐SD, was associated with a reduction in the rate of all‐cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76‐0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55‐1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76‐1.01), pinteraction = 0.62]. Among those with diabetes, QIV‐HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04‐0.83)] but had no effect on ∆HbA1c; QIV‐HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (−0.9 to 1.2). QIV‐HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94‐1.47)].ConclusionsIn this post‐hoc analysis, QIV‐HD versus QIV‐SD was associated with an increased rVE against the composite of all‐cause death and hospitalization for pneumonia/influenza, and the all‐cause hospitalization rate irrespective of diabetes status.