Recombinant Zoster Vaccine Significantly Reduces the Impact on Quality of Life Caused by Herpes Zoster in Adult Autologous Hematopoietic Stem Cell Transplant Recipients: A Randomized Placebo-Controlled Trial (ZOE-HSCT)

Desmond Curran, Sean Matthews, Scott D. Rowley, Jo Anne H. Young, Adriana Bastidas, Achilles Anagnostopoulos, Ibrahim Barista, Pranatharthi Haran Chandrasekar, Michael Dickinson, Mohamed El Idrissi, Inmaculada Heras, Samuel T. Milliken, Jorge Monserrat Coll, María Belén Navarro Matilla, Lidia Oostvogels, Beata Piątkowska-Jakubas, Dimas Quiel, Waleed Sabry, Stefan Schwartz, Dominik L.D. SelleslagKeith M. Sullivan, Koen Theunissen, Zeynep Arzu Yegin, Su Peng Yeh, Francesco Zaja, Jeff Szer

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Herpes zoster (HZ) can have a substantial impact on quality of life (QoL). The vaccine efficacy (VE) of a recombinant zoster vaccine (RZV) was 68.2% (95% confidence interval [CI], 55.6% to 77.5%) in a phase 3 study in adult autologous hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). Herein, we report the impact of RZV on patients’ QoL. Autologous HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1 to 2 months apart. QoL was measured by the Short Form Survey-36 and Euro-QoL-5 Dimension at baseline, 1 month, and 1 year postdose 2 and during suspected HZ episodes with the Zoster Brief Pain Inventory (ZBPI). The RZV impact on ZBPI burden of illness and burden of interference scores was estimated. The 2 scores were calculated from the area under the curve (days 0 to 182) of the ZBPI worst pain and ZBPI activities of daily living scores, respectively, assuming a score of 0 for patients not having a confirmed HZ episode. The ZBPI maximum worst pain score was significantly lower in the RZV than placebo group (mean: 5.8 versus 7.1, P = .011). Consequently, the VE estimates for HZ burden of illness (82.5%; 95% CI, 73.6 to 91.4) and burden of interference (82.8%; 95% CI, 73.3 to 92.3) were higher than the HZ VE estimate (ie, 68.2%). RZV showed significantly better QoL scores than placebo 1 week following rash onset among patients with confirmed HZ. In addition to reducing the risk of HZ and its complications, RZV significantly reduced the impact of HZ on patients’ QoL in those who developed breakthrough disease.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - 2019

Bibliographical note

Funding Information:
The authors would like to thank the study participants, investigators, and study teams involved in this trial, as well as Anne Schuind for her comments during review and Christophe Sauboin, Camelia Marcos, and Thomas C. Heineman for the patient-reported outcome questionnaire selection (ie, ZBPI, EQ-5D, and SF-36), which was included in the ZOE-HSCT clinical trial. Medical writing services were provided by Julia Donnelly (freelancer on behalf of GSK). Editorial assistance and publication coordination were provided by Sara Blancquaert (Modis on behalf of GSK). Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Financial disclosure: This work was funded by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA was involved in all stages of the study and covered all costs associated with developing and publishing this manuscript. Declaration of Competing Interest: During the conduct of the study, J.M.C. reports data monitoring board fees from the GSK group of companies. S.S. reports reimbursement for treatment and monitoring of study participants from the GSK group of companies. K.M.S. reports a grant and personal fees from the GSK group of companies and from NIAID, NIH awarded to Duke University. J.A.Y. reports reimbursement from the GSK group of companies to the University of Minnesota for participant enrollment. Outside the submitted work, A.A. reports grants from MERCK. S.D.R. reports consultant fees from Incyte, Fate Therapeutics, and Mesoblast. S.S. reports personal fees and nonfinancial support from AMGEN, Basilea Pharmaceutica, Gilead, Jazz Pharmaceuticals, MSD Sharp & Dohme, and Pfizer. K.M.S. reports personal fees from Kiadis Pharmaceutical and Roche Genentech. J.S. reports personal fees from Novartis; nonfinancial support from Pfizer, Sanofi Genzyme, and Shire; and grants, personal fees, and nonfinancial support from Alexion. F.Z. reports consultancy fees from Abbvie, Celgene, Gilead, Janssen, Novartis, Roche, and Sandoz; payment for lectures including service on speakers bureaus from Abbvie, Amgen, BMS, Celgene, Gilead, Janssen, Novartis, and Roche; payment for development of educational presentations from Novartis; and travel/accommodations/meeting expenses unrelated to activities listed (eg, consultancy) from Amgen, Celgene, Novartis, Roche, and Takeda. D.C. and M.E.I. are employees of the GSK group of companies. D.C. owns stock options, and M.E.I. owns stock from the GSK group of companies. S.M. works as a freelance consultant on behalf of the GSK group of companies. A.B. and L.O. were employees of the GSK group of companies during the conduct of the study and continue to own stock from the GSK group of companies. A.B. is an employee of Mithra Pharmaceuticals as of June 17, 2019. L.O. is an employee of CureVac AG as of March 1, 2018; continues to own stock from the GSK group of companies; and is inventor on a patent owned by the GSK group of companies and relevant to the recombinant zoster vaccine. I.B. P.H.C. M.D. I.H. S.T.M. M.B.N.M. B.P-J. D.Q. W.S. D.L.D.S. K.T. Z.A.Y. and S.-P.Y. have nothing to disclose. Authorship statement: A.B. D.C. M.E.I. S.T.M. L.O. and K.M.S. conceived and designed the study. A.A. I.B. A.B. P.H.C. M.D. S.T.M. J.M.C. M.B.N.M. B.P.-J. D.Q. S.D.R. W.S. S.S. D.L.D.S. K.M.S. J.S. K.T. Z.A.Y. S.-P.Y. J.A.H.Y. and F.Z. collected or generated study data. A.A. A.B. P.H.C. D.C. M.D. S.T.M. J.M.C. M.B.N.M. B.P.-J. D.Q. S.D.R. W.S. S.S. D.L.D.S. K.M.S. J.S. K.T. Z.A.Y. S.-P.Y. J.A.H.Y. and F.Z. performed the study. A.B. D.C. M.D. S.D.R. W.S. D.L.D.S. K.M.S. S.-P.Y. J.A.H.Y. and F.Z. contributed materials/analysis/reagent tools. A.B. D.C. M.E.I. S.M. L.O. S.D.R. S.S. K.M.S. J.S. K.T. and F.Z. were involved in the analysis or interpretation of the data. All authors contributed to the writing/reviewing of the manuscript and approved the final version for submission. All authors vouch for the completeness and accuracy of all the data and the presented analyses. Financial disclosure: See Acknowledgments on page 7.

Funding Information:
Financial disclosure: This work was funded by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA was involved in all stages of the study and covered all costs associated with developing and publishing this manuscript.

Funding Information:
Declaration of Competing Interest: During the conduct of the study, J.M.C. reports data monitoring board fees from the GSK group of companies. S.S. reports reimbursement for treatment and monitoring of study participants from the GSK group of companies. K.M.S. reports a grant and personal fees from the GSK group of companies and from NIAID, NIH awarded to Duke University. J.A.Y. reports reimbursement from the GSK group of companies to the University of Minnesota for participant enrollment. Outside the submitted work, A.A. reports grants from MERCK. S.D.R. reports consultant fees from Incyte, Fate Therapeutics, and Mesoblast. S.S. reports personal fees and nonfinancial support from AMGEN, Basilea Pharmaceutica , Gilead, Jazz Pharmaceuticals , MSD Sharp & Dohme, and Pfizer . K.M.S. reports personal fees from Kiadis Pharmaceutical and Roche Genentech. J.S. reports personal fees from Novartis; nonfinancial support from Pfizer , Sanofi Genzyme , and Shire ; and grants, personal fees, and nonfinancial support from Alexion. F.Z. reports consultancy fees from Abbvie, Celgene, Gilead, Janssen, Novartis, Roche, and Sandoz; payment for lectures including service on speakers bureaus from Abbvie, Amgen, BMS, Celgene, Gilead, Janssen, Novartis, and Roche; payment for development of educational presentations from Novartis; and travel/accommodations/meeting expenses unrelated to activities listed (eg, consultancy) from Amgen, Celgene, Novartis, Roche, and Takeda. D.C. and M.E.I. are employees of the GSK group of companies. D.C. owns stock options, and M.E.I. owns stock from the GSK group of companies. S.M. works as a freelance consultant on behalf of the GSK group of companies. A.B. and L.O. were employees of the GSK group of companies during the conduct of the study and continue to own stock from the GSK group of companies. A.B. is an employee of Mithra Pharmaceuticals as of June 17, 2019. L.O. is an employee of CureVac AG as of March 1, 2018; continues to own stock from the GSK group of companies; and is inventor on a patent owned by the GSK group of companies and relevant to the recombinant zoster vaccine. I.B., P.H.C., M.D., I.H., S.T.M., M.B.N.M., B.P-J., D.Q., W.S., D.L.D.S., K.T., Z.A.Y., and S.-P.Y. have nothing to disclose.

Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy

Keywords

  • Autologous hematopoietic stem cell transplant
  • Herpes zoster
  • Quality of life
  • Recombinant zoster vaccine
  • Vaccination

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