RESUMO
Background: Previous phase 3 studies showed that the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) is well tolerated and efficacious in preventing RSV-associated lower respiratory tract disease in adults ≥ 60 years of age. This study evaluated lot-to-lot immunogenicity consistency, reactogenicity, and safety of three RSVPreF3 OA lots. Methods: This phase 3, multicenter, double-blind study randomized (1:1:1) participants ≥ 60 years of age to receive one of three RSVPreF3 OA lots. Serum RSVPreF3-binding immunoglobulin G (IgG) concentration was assessed at baseline and 30 days post-vaccination. Lot-to-lot consistency was demonstrated if the two-sided 95 % confidence intervals (CIs) of the RSVPreF3-binding IgG geometric mean concentration (GMC) ratios between each lot pair at 30 days post-vaccination were within 0.67 and 1.50. Solicited adverse events (AEs) within four days, unsolicited AEs within 30 days, and serious AEs (SAEs) and potential immune-mediated diseases within six months post-vaccination were recorded. Results: A total of 757 participants received RSVPreF3 OA, of whom 708 were included in the per-protocol set (234, 237, and 237 participants for each lot). Lot-to-lot consistency was demonstrated: GMC ratios were 1.06 (95 % CI: 0.94-1.21), 0.92 (0.81-1.04), and 0.87 (0.77-0.99) between the lot pairs (lot 1/2; 1/3; 2/3). For the three lots, the RSVPreF3-binding IgG concentration increased 11.84-, 11.29-, and 12.46-fold post-vaccination compared to baseline. The reporting rates of solicited and unsolicited AEs, SAEs, and potential immune-mediated diseases were balanced between lots. Twenty-one participants reported SAEs; one of these-a case of atrial fibrillation-was considered by the investigator as vaccine-related. SAEs with a fatal outcome were reported for four participants, none of which were considered by the investigator as vaccine-related. Conclusion: This study demonstrated lot-to-lot immunogenicity consistency of three RSVPreF3 OA vaccine lots and indicated that the vaccine had an acceptable safety profile.ClinicalTrials.gov: NCT05059301.
RESUMO
AIM: The aim of the present study was to investigate bleeding adverse drug reactions (ADRs) in patients exposed to serotonin reuptake inhibitors (SRI) plus antiplatelet agents using the French Pharmacovigilance Database (FPVDB) regarding the controversial data in the literature. METHODS: The case/non-case method was used to measure the association between bleedings and exposure to SRIs plus antiplatelet agents versus antiplatelet drugs alone. RESULTS: Over 3 years, a total of 1,977 spontaneous reports of ADRs were collected with antiplatelet drugs, and antiplatelet agents plus SRIs in patients aged over 50 years, of which 1,331 (67.3 %) concerned bleeding. Multivariate logistic regression analysis failed to show any significant association [adjusted ROR = 0.8 (0.5-1.2)]. CONCLUSION: The data did not demonstrate any significant association between bleeding ADRs and exposure to SRI + antiplatelet agents versus antiplatelets alone. Considering other conflicting results, this risk should be kept in mind by physicians when treating patients with several risk factors.
