Long-term persistence of zoster vaccine efficacy

Abstract

Background: The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination.

Methods: Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups.

Results: The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8.

Conclusions: Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.

Keywords: herpes zoster; herpes zoster burden of illness; herpes zoster vaccine; persistence of vaccine efficacy; postherpetic neuralgia.

Figure 1.

Screening, enrollment and disposition of participants in the Long-Term Persistence Substudy (LTPS). ^aDuring LTPS, 453 Shingles Prevention Study (SPS) zoster vaccine recipients who did not enroll in the Short-Term Persistence Substudy (STPS) were screened for LTPS, and 321 were enrolled; ^bTwo hundred fifty-four participants were withdrawn, died, or were lost to follow-up in STPS before screening in LTPS; ^cParticipants may have had >1 reason for not enrolling in LTPS. Participants who withdrew from STPS and were not enrolled in LTPS are not counted in the screened population.

Figure 2.

Vaccine efficacy for the 3 study outcomes in the Long-Term Persistence Substudy—primary analysis and sensitivity analyses. A, Vaccine efficacy for herpes zoster (HZ) burden of illness (BOI). B, Vaccine efficacy for the incidence of postherpetic neuralgia (PHN). C, Vaccine efficacy for the incidence of HZ. Estimates of vaccine efficacy are plotted with 95% confidence intervals. For the primary vaccine efficacy analysis, the historical model placebo control group only incorporated data from the Shingles Prevention Study (SPS) and was adjusted to include the calendar effect on the incidence of HZ observed in the placebo group in the SPS. For sensitivity analysis I (conservative assumptions), the historical model placebo control group incorporated only data from the SPS and did not include the calendar effect observed in the SPS. For sensitivity analysis II (contemporary assumptions), the historical model placebo control group incorporated data from both the SPS and the Short-Term Persistence Substudy, and was also adjusted for the calendar effect on the incidence of HZ observed in the placebo groups of the 2 studies. ^†Sensitivity analysis I for vaccine efficacy for incidence of PHN yielded the same result as the primary analysis, as there was no calendar effect adjustment for the incidence of PHN.

Figure 3.

Vaccine efficacy for the 3 study outcomes by year postvaccination. A, Vaccine efficacy for herpes zoster (HZ) burden of illness (BOI). B, Vaccine efficacy for incidence of postherpetic neuralgia (PHN).

C, Vaccine efficacy for incidence of HZ. Estimates of vaccine efficacy are plotted with 95% confidence intervals. Results from the Shingles Prevention Study (SPS) and Short-Term Persistence Substudy (STPS) were previously published [2, 4]. For the primary vaccine efficacy analysis, the historical model placebo control group only incorporated data from the SPS and was adjusted to include the calendar effect on the incidence of HZ observed in the placebo group in the SPS. For sensitivity analysis I (conservative assumptions), the historical model placebo control group incorporated only data from SPS and did not include the calendar effect on the incidence of HZ observed in the SPS. For sensitivity analysis II (contemporary assumptions), the historical model placebo control group incorporated data from both the SPS and the STPS, and was also adjusted for the calendar effect on the incidence of HZ observed in the placebo groups of the 2 studies. For year 4, person-years were 97% from SPS and 3% from STPS. For year 5, person years were 16% from SPS and 84% from STPS. For years 6, 100% of the events and person-years were from STPS subjects. *Data for years 5–6 from the Long-Term Persistence Substudy (LTPS) are excluded; ^#For years 7 and 8, both STPS and LTPS contribute vaccine group data. Vaccine efficacy for primary and sensitivity analyses in years 7 to 11 include only data from the LTPS.