High-dose vs standard-dose influenza vaccine in older adults according to diabetes status, a prespecified analysis of the FLUNITY-HD study

Background The FLUNITY-HD study, pooled analysis including 466,320 randomized older adults, demonstrated that high-dose inactivated influenza vaccine (HD-IIV) provided proven superior protection against hospitalization outcomes than standard-dose inactivated influenza vaccine (SD-IIV) among adults aged ≥65 years. Whether the relative vaccine effectiveness (rVE) varies according to diabetes status remains incompletely characterized. Methods Prespecified analysis within FLUNITY-HD evaluating rVE by baseline diabetes status conducted using pooled data from two harmonized randomized trials in Denmark (DANFLU-2) and Spain (GALFLU). Healthcare data were used for outcome ascertainment, with follow-up from 14 days post-vaccination through May 31 of the following year.Primary outcome was hospitalization for influenza or pneumonia. Secondary and exploratory outcomes included respiratory, cardiovascular, all-cause hospitalization, and mortality. Treatment effects were assessed stratified by diabetes. Results A total of 466,320 individually randomized participants were included in the analysis (233,311 HD-IIV; 233,009 SD-IIV), 64,981 (13.9%) had diabetes at baseline. Mean age was 73.3 years (SD 5.4) overall and 73.6 years (SD 5.4) in the diabetic group. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 638 (0.98%) participants with diabetes vs. 2,111 (0.52%) participants without diabetes. HD-IIV significantly reduced the risk of the primary endpoint versus SD-IIV (rVE 8.8%; 95% CI 1.7–15.5; P=0.0082), with no evidence of effect modification by diabetes status (P for interaction = 0.81), Figure 1. Compared with the SD-IIV group, the HD-IIV group experienced a significantly lower incidence of hospitalization for cardiorespiratory disease, laboratory confirmed influenza, all cause hospitalization and hospitalization for influenza, with no effect modification by diabetes status (all P interaction ≥ 0.37). Number Needed to Vaccinate (NNV) was lower among diabetic participants for all hospitalization related outcomes, as low as 376 needed to switch from SD-IIV to HD-IIV to avert one all-cause hospitalization, Figure 1. HD-IIV reduced the incidence of hospitalization for any cardiovascular disease and hospitalisation for heart failure, with no effect modification by diabetes status (P-interaction 0.33 and 0.72). Diabetes did not modify the association with cardiovascular related hospitalizations,except for a modest heterogeneity for atrial fibrillation hospitalization (P interaction=0.05), Figure 2. Conclusion HD-IIV provided superior protection against hospitalization compared with SD-IIV, with consistent effect observed regardless of diabetes status. Individuals with diabetes experienced greater absolute benefit, with lower NNV per outcome averted for HD-IIV. Findings support the public-health value of HD-IIV regardeless of diabetes, with potentially greater absolute benefit in diabetes participants.