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 ain. 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. [GRAPHICS] PLAIN LANGUAGE SUMMARY Shingles is a viral disease caused by the reactivation of the varicella virus in adults. Symptoms include a painful rash that shows up on the side of the body. Researchers conducted three large phase III clinical trials in immunocompetent individuals aged 50 years and older and in adult immunocompromised patients using similar methodologies for study design, case definition, data collection, and analysis in these populations. This post hoc analysis from these three large phase III clinical trials analyzed the incidence of shingles and the rash and pain characteristics in adults who received placebo instead of vaccination with recombinant zoster vaccine. Immunocompetent individuals aged 50 years and older showed a high incidence of shingles, and this was even more pronounced in immunocompromised adults aged 18 years and older. Most adults with shingles had severe pain. Immunocompromised patients more frequently had long-lasting pain (post-herpetic neuralgia). Adults aged 50 years and older most frequently had a rash on the upper trunk while immunocompromised patients most frequently had a rash on the lower trunk. This study showed the high impact of shingles, especially in immunocompromised patients. Vaccination is recommended in older adults (more than 50 years) and in adult immunocompromised populations.