Final analysis of the ZOE-LTFU trial to 11 years post-vaccination: efficacy of the adjuvanted recombinant zoster vaccine against herpes zoster and related complications
Ana Strezova, Javier Díez‐Domingo, Anthony L. Cunningham, Takashi Eto, Charles P. Andrews, Clovis Arns, Eun Ju Choo, David S.C. Hui, Giancarlo Icardi, Shelly McNeil, Airi Põder, Pavel Kosina, Lars Rombo, Tino F. Schwarz, Juan Carlos Tinoco, Chong‐Jen Yu, Jing Wang, Jyoti Soni, Manyee Tsang, Rafael León, Agnes Mwakingwe-Omari, Abul Kashem Munir, Agnes Csuth, Agnes Himpel-Boenninghoff, Aino Forsten, Airi Poder, Ake Olsson, Alain Baty, Alain Boye, Alen Jambrecina, Alex Rodríguez Badia, Alexander Thompson, Andrea Gori, Anitta Ahonen, Anna Vilella Morato, Anthony Cunningham, Antje Dahmen, Axel Schaefer, Azhar Toma, Barry Lubin, Beate Moeckesch, Beatrice Gerlach, Benita Ukkonen, Benjamin Lasko, Benoit Daguzan, Bernhard Schmitt, Bo Liu, Brian Webster, Bruce Rankin, Calvin Powell, Carlos Brotons Cuixart, Carol Pretswell, Catherine Vaillancourt, Cecil Farrington, Charles Andrews, Chester Fisher, Chigomezgo Munthali, Chiu-Shong Liu, Chong-Jen Yu, Christian Duroy, Christian Schubert, Christiane Klein, Christine Cerna, Christine Grigat, Christophe Genies, Christopher Lucasti, Cláudia Murta de Oliveira, Claus Keller, Clovis Cunha, Concepcion Nunez Lopez, Covadonga Caso, Cristiano Zerbini, Dae Won Park, Damien Mcnally, Dan Curiac, David Francyk, David García Vidal, David Shu Cheong Hui, Denis Taminau, Domenico Montu, Dominique Saillard, Donald Quinn, Duane Wombolt, Edmund Kwok Yiu Sha, Elina Sirnela-Rif, Elisabeth Barberan, Eric St-Amour, Eriko Kinugasa, Ernie Riffer, Essam Abdulhakim, Eugene Athan, Eun-Ju Choo, Eva Ackefelt Frick, Felix Proepper, Ferdinandus de Looze, Francesco Schioppa, François Brault, Frederick Martin, Gabriele Illies, Georg Plassmann
Abstract
Background: Herpes zoster (HZ) vaccines should provide durable protection against HZ and HZ-related complications. We report the final analysis of a long-term follow-up (LTFU) study (ZOE-LTFU) including 11 years of follow-up after primary vaccination with recombinant zoster vaccine (RZV). Methods: ZOE-LTFU (NCT02723773) was an open-label, phase 3b study following participants of two phase 3 trials, ZOE-50 and ZOE-70. ZOE-LTFU started approximately 5 years post-vaccination in ZOE-50/70 and participants were followed for 6 years. The primary objective was to assess vaccine efficacy (VE) against HZ during ZOE-LTFU. Secondary objectives included VE against HZ from 1 month post-dose 2 in ZOE-50/70 until end of ZOE-LTFU, VE against post-herpetic neuralgia (PHN) and non-PHN complications, immunogenicity, and long-term safety. The VE calculation used a historical control constructed with ZOE-50/70 placebo data. Findings: VE was assessed in the modified total vaccinated cohort (n = 7273 [mean age 67·3 years at first vaccination]). During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. From 1 month post-dose 2 in ZOE-50/70 to the end of ZOE-LTFU, VE against HZ was 87·7% (95% CI: 84·9, 90·1) in participants ≥50 years and sustained at 82·0% (95% CI: 63·0, 92·2) in the eleventh year post-vaccination. Humoural and cell-mediated immune responses plateaued at over 5-fold and ∼7-fold, respectively, above pre-vaccination levels in ZOE-50/70. No RZV-related serious adverse events occurred. Interpretation: Efficacy of RZV against HZ and associated complications remained high through 11 years post-vaccination, indicating sustained clinical benefit. Funding: The funder of the study was GSK who was involved in study design, data collection, data analysis, data interpretation, writing of the report, and the decision to submit for publication.