A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults)

Abstract

Background: The Community Acquired Pneumonia immunization Trial in Adults (CAPiTA) was conducted to evaluate 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) in adults aged ≥65 years. Plotting the cumulative number of episodes against time from vaccination demonstrated that efficacy was evident soon after vaccination and persisted throughout the duration of the study. This post hoc analysis was performed to quantify the persistence of vaccine efficacy (VE) of PCV13. Methods: This was a parallel-group, randomized, placebo-controlled, double-blind trial. Subjects were enrolled between September 15, 2008 and January 30, 2010 at 101 sites in the Netherlands and randomized 1:1 to receive a single dose of PCV13 or placebo. The observed accumulation of episodes for VT-CAP, nonbacteremic/noninvasive VT-CAP (NB/NI-VT-CAP), and VT-IPD over the course of the study after vaccination was assessed. Post hoc time-to-event analyses of primary and secondary endpoints were performed. VE behavior over time was derived and effects of treatment, time, and time by treatment interactions were estimated. Results: A total of 84,496 individuals were enrolled (PCV13, n = 42,240; placebo, n = 42,256). Cases of VT-CAP, NB/NI-VT-CAP, and VT-IPD were greater among placebo recipients compared with PCV13 recipients throughout the postvaccination observation period with a periodic rise in cases in the placebo group that was consistent with varied exposure and ensuing disease over time. There was a significant difference in disease-free survival among PCV13 recipients compared with placebo recipients for VT-CAP (log-rank test P = 0.0005), NB/NI VT-CAP (P = 0.0051), and VT-IPD (P = 0.0004). VE ranged from 42.9% to 50.0% for VT-CAP, 36.2% to 48.5% for NB/NI-VT-CAP, and 66.7% to 75.0% for VT-IPD. Conclusions: The results of this post hoc analysis of the persistence of PCV13 VE in adults ≥65 years, indicate that PCV13 was protective over the 5-year duration of the study, with no waning of efficacy observed. ClinicalTrials.gov identifier NCT00744263.