Natural History of Herpes Zoster in the Placebo Groups of Three Randomized Phase III Clinical Trials

Introduction The risk of herpes zoster (HZ) is associated with a decline in immune system function, linked to aging and/or immunocompromising or immunosuppressive diseases or therapies. In this post hoc analysis we describe the incidence of HZ, rash characteristics, and burden of HZ pain in immunocompetent adults ≥ 50 years of age (YOA) and in hematopoietic stem cell transplantation (HSCT) recipients ≥ 18 YOA. Methods ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) were phase III, observer-blind, placebo-controlled, randomized studies conducted in immunocompetent adults ≥ 50 YOA and ≥ 70 YOA; and in HSCT recipients ≥ 18 YOA, respectively. A similar methodology for study design, case definition, and data collection were applied in all three studies. The participants received either two doses of the adjuvanted recombinant zoster vaccine or placebo, 1–2 months apart. This analysis focuses on all confirmed HZ cases from the placebo groups of the three studies. HZ pain and interference with activities of daily living were assessed using the Zoster Brief Pain Inventory instrument. Results Overall, 280, 240, and 172 placebo participants with an HZ confirmed episode aged ≥ 50, ≥ 70, and ≥ 18 YOA were included in the ZOE-50, ZOE-70, and ZOE-HSCT analyses, respectively. The incidence of HZ was 9.1/1000 person-years in both the ZOE-50 and ZOE-70 placebo groups and 95.6/1000 person-years in the ZOE-HSCT study placebo group. In the three studies, most individuals with HZ had severe pain, with approximately 90% of individuals reporting clinically significant pain. An estimated 12.3%, 16.9%, and 21.8% of patients in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, developed post-herpetic neuralgia. Conclusion The incidence and burden of HZ is high in immunocompetent adults aged ≥ 50 YOA and even more so in HSCT recipients aged ≥ 18 YOA. Graphical Abstract