Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine: a pooled post-hoc analysis of two parallel randomized trials

Figures & data

Table 1. Demographic characteristics (pooled ZOE-50/70 modified Total Vaccinated Cohort)

	RZV (N = 13,881)	Placebo (N = 14,035)
Age (years)
Mean age at first dose ± SD	68.5 ± 9.8	68.5 ± 9.8
Gender, n (%)
Female	8,044 (57.9)	8,178 (58.3)
Male	5,837 (42.1)	5,857 (41.7)
Geographic ancestry, n (%)
White – Caucasian/European	10,321 (74.4)	10,403 (74.1)
Asian – East Asian	1,908 (13.7)	1,926 (13.7)
Asian – Japanese Heritage	575 (4.1)	591 (4.2)
African/African American	200 (1.4)	183 (1.3)
Other	877 (6.3)	932 (6.6)
Selected medical conditions present at enrollment, n (%)
Hypertension	7,206 (51.9)	7,226 (51.5)
Osteoarthritis and/or vertebral disorders	4,951 (35.7)	5,032 (35.9)
Dyslipidemia	4,628 (33.3)	4,707 (33.5)
Diabetes	2,350 (16.9)	2,372 (16.9)
Osteoporosis/Osteopenia	1,481 (10.7)	1,528 (10.9)
Gastroesophageal reflux disease	1,334 (9.6)	1,313 (9.4)
Sleep disorder	1,304 (9.4)	1,309 (9.3)
Prostatic diseases	1,244 (9.0)	1,285 (9.2)
Hypothyroidism	1,167 (8.4)	1,147 (8.2)
Depression	1,017 (7.3)	987 (7.0)
Coronary heart disease	1,003 (7.2)	1,055 (7.5)
Cataract	782 (5.6)	800 (5.7)
Asthma	646 (4.7)	689 (4.9)
Respiratory disorders^#	614 (4.4)	560 (4.0)
Renal disorders	308 (2.2)	300 (2.1)

RZV = participants receiving the adjuvanted recombinant zoster vaccine; Placebo = participants receiving placebo; ZOE-50/70 = RZV efficacy studies in adults ≥50 YOA (NCT01165177) and ≥70 YOA (NCT01165229); N = number of participants in the pooled modified total vaccinated cohorts; n (%) = number (percentage) of participants in each category; SD = standard deviation.

^#Other than asthma.

Figure 1. Participant flow (pooled ZOE-50/70 studies) RZV = participants receiving the adjuvanted recombinant zoster vaccine; Placebo = participants receiving placebo; ZOE-50/70 = RZV efficacy studies in adults ≥50 YOA (NCT01165177) and ≥70 YOA (NCT01165229), respectively; (m)TVC = (modified) total vaccinated cohort; HZ, herpes zoster

Table 2. Vaccine efficacy against first or only episode of herpes zoster in ZOE-50/70 participants reporting at least 1 of the 15 selected medical conditions at enrollment (pooled modified Total Vaccinated Cohort)

	RZV				Placebo
	N	n	Cumulative follow-up py	Rate of HZ cases/ 1,000 py	N	n	Cumulative follow-up py	Rate of HZ cases/ 1,000 py	Vaccine efficacy % (95% CI)
Selected medical conditions present at enrollment
Hypertension	7,206	21	27,202.9	0.8	7,226	254	26,752.4	9.5	91.9 (87.3–95.1)
Osteoarthritis and/or vertebral disorders	4,951	16	18,732.8	0.9	5,032	178	18,604.4	9.6	91.1 (85.1–95.0)
Dyslipidemia	4,628	15	17578.0	0.9	4,707	169	17,507.2	9.7	91.2 (85.1–95.2)
Diabetes	2,350	7	8,723.8	0.8	2,372	80	8,652.7	9.2	91.2 (81.1–96.6)
Osteoporosis/Osteopenia	1,481	5	5,551.7	0.9	1,528	72	5,552.1	13.0	92.9 (82.7–97.8)
Gastroesophageal reflux disease	1,334	6	5,009.7	1.2	1,313	44	4,816.2	9.1	86.9 (69.0–95.4)
Sleep disorder	1,304	4	4,899.3	0.8	1,309	56	4,803.3	11.7	93.1 (81.4–98.2)
Prostatic diseases	1,244	2	4,648.4	0.4	1,285	50	4,667.0	10.7	96.1 (85.1–99.5)
Hypothyroidism	1,167	4	4,387.0	0.9	1,147	28	4,241.0	6.6	86.2 (60.4–96.5)
Depression	1,017	2	3,767.1	0.5	987	29	3,567.5	8.1	93.4 (74.1–99.2)
Coronary heart disease	1,003	1	3,773.8	0.3	1,055	35	3,912.8	8.9	97.0 (82.3–99.9)
Cataract	782	4	2,964.7	1.3	800	41	2,931.0	14.0	90.4 (73.4–97.5)
Asthma	646	3	2,420.9	1.2	689	28	2,575.8	10.9	88.8 (63.6–97.8)
Respiratory disorders^#	614	3	2,220.5	1.4	560	17	1,944.4	8.7	84.5 (46.4–97.1)
Renal disorders	308	1	1,064.8	0.9	300	7	1,001.5	7.0	86.6 (-4.5–99.7)
Number of selected medical conditions present at enrollment
1	3,159	5	12,269.2	0.4	3,211	109	12,213.4	8.9	95.4 (89.0–98.5)
2	3,080	7	11,797.1	0.6	3,117	97	11,746.4	8.3	92.8 (84.7–97.2)
3	2,316	8	8,803.7	0.9	2,455	88	9,162.6	9.6	90.5 (80.5–96.0)
At least 3	5,188	19	19,417.0	1.0	5,280	199	19,338.4	10.3	90.5 (84.8–94.4)
At least 4	2,872	11	10,613.3	1.0	2,825	111	10,175.8	10.9	90.6 (82.4–95.4)
At least 5	1,406	5	5,132.5	1.0	1,350	52	4,742.4	11.0	91.2 (78.0–97.3)
At least 6	569	2	2,039.2	1.0	551	20	1,910.1	10.5	90.9 (62.5–99.0)

RZV = participants receiving the adjuvanted recombinant zoster vaccine; Placebo = participants receiving placebo; ZOE-50/70 = RZV efficacy studies in adults ≥50 YOA (NCT01165177) and ≥70 YOA (NCT01165229), respectively; N = number of participants in each category; n = number of confirmed first or only herpes zoster case; HZ, herpes zoster; CI = confidence interval; py = person years. The follow-up period was censored at the first occurrence of a confirmed HZ episode.

^#Other than asthma.

Table 3. Safety of RZV in ZOE-50/70 participants reporting at least 1 of the 15 selected medical conditions at enrollment (pooled Total Vaccinated Cohort)

			Reported from dose 1 until 1 year post-dose 2		Reported during the whole post-vaccination period
	Number of participants in the TVC		SAEs		Deaths		pIMDs
	RZV	Placebo	RZV % (95% CI)	Placebo % (95% CI)	RZV % (95% CI)	Placebo % (95% CI)	RZV % (95% CI)	Placebo % (95% CI)
Selected medical conditions present at enrollment
Hypertension	7,609	7,556	12.5 (11.8–13.3)	12.6 (11.9–13.4)	5.7 (5.2–6.3)	6.3 (5.7–6.8)	1.2 (1.0–1.5)	1.2 (0.9–1.4)
Osteoarthritis and/or vertebral disorders	5,212	5,258	12.5 (11.6–13.4)	13.2 (12.3–14.1)	5.1 (4.5–5.7)	5.5 (4.9–6.1)	1.5 (1.2–1.8)	1.7 (1.4–2.1)
Dyslipidemia	4,904	4,953	12.1 (11.2–13.0)	12.1 (11.2–13.0)	4.7 (4.1–5.3)	4.5 (4.0–5.1)	1.1 (0.8–1.4)	1.6 (1.3–2.0)
Diabetes	2,480	2,502	15.2 (13.8–16.7)	15.4 (14.0–16.9)	7.3 (6.3–8.4)	8.3 (7.2–9.4)	1.0 (0.6–1.4)	1.3 (0.9–1.8)
Osteoporosis/Osteopenia	1,568	1,592	11.9 (10.4–13.6)	12.9 (11.3–14.6)	5.2 (4.1–6.4)	5.2 (4.2–6.4)	1.3 (0.8–2.0)	1.8 (1.2–2.5)
Gastroesophageal reflux disease	1,407	1,374	14.4 (12.6–16.4)	15.1 (13.2–17.1)	4.3 (3.3–5.5)	5.6 (4.4–7.0)	1.1 (0.7–1.8)	2.3 (1.6–3.3)
Sleep disorder	1,379	1,389	13.6 (11.9–15.6)	13.0 (11.2–14.8)	6.6 (5.3–8.0)	7.3 (6.0–8.8)	1.5 (0.9–2.3)	1.7 (1.1–2.5)
Prostatic diseases	1,319	1,353	16.6 (14.6–18.7)	16.5 (14.5–18.6)	8.3 (6.9–10.0)	7.8 (6.4–9.3)	0.8 (0.4–1.5)	1.5 (0.9–2.3)
Hypothyroidism	1,218	1,208	11.2 (9.5–13.2)	12.3 (10.5–14.3)	3.4 (2.5–4.6)	4.0 (2.9–5.2)	1.9 (1.2–2.8)	1.8 (1.1–2.7)
Depression	1,095	1,070	14.2 (12.2–16.5)	15.4 (13.3–17.7)	6.1 (4.8–7.7)	5.3 (4.1–6.8)	1.0 (0.5–1.8)	1.1 (0.6–2.0)
Coronary heart disease	1,065	1,097	20.4 (18.0–22.9)	20.3 (18.0–22.8)	8.6 (7.0–10.5)	9.3 (7.6–11.2)	1.0 (0.5–1.8)	0.9 (0.4–1.7)
Cataract	828	836	13.8 (11.5–16.3)	13.2 (10.9–15.6)	5.1 (3.7–6.8)	6.8 (5.2–8.7)	1.0 (0.4–1.9)	0.8 (0.3–1.7)
Asthma	698	714	15.3 (12.7–18.2)	12.9 (10.5–15.6)	4.4 (3.0–6.2)	4.2 (2.9–5.9)	2.3 (1.3–3.7)	2.5 (1.5–4.0)
Respiratory disorders^#	651	593	20.0 (17.0–23.3)	23.1 (19.8–26.7)	13.4 (10.8–16.2)	15.0 (12.2–18.1)	0.6 (0.2–1.6)	2.0 (1.0–3.5)
Renal disorders	328	319	26.2 (21.5–31.3)	23.5 (19.0–28.6)	15.2 (11.5–19.6)	15.7 (11.9–20.1)	0.6 (0.1–2.2)	1.3 (0.3–3.2)
Number of selected medical conditions present at enrollment
1	3,309	3,333	6.9 (6.0–7.8)	7.7 (6.8–8.7)	3.2 (2.6–3.9)	3.4 (2.8–4.0)	1.4 (1.0–1.9)	1.2 (0.9–1.7)
2	3,267	3,238	9.7 (8.7–10.8)	9.7 (8.7–10.8)	3.9 (3.3–4.6)	4.5 (3.8–5.3)	1.3 (1.0–1.8)	1.6 (1.2–2.1)
3	2,449	2,567	12.0 (10.7–13.3)	13.0 (11.7–14.3)	5.6 (4.7–6.5)	5.8 (5.0–6.8)	1.2 (0.8–1.7)	1.2 (0.8–1.7)
At least 3	5,487	5,555	14.7 (13.8–15.7)	14.8 (13.9–15.8)	6.4 (5.8–7.1)	6.7 (6.0–7.3)	1.2 (0.9–1.5)	1.5 (1.2–1.8)
At least 4	3,038	2,988	16.9 (15.6–18.3)	16.4 (15.1–17.7)	7.1 (6.3–8.1)	7.4 (6.5–8.4)	1.2 (0.8–1.6)	1.7 (1.2–2.2)
At least 5	1,490	1,430	19.8 (17.8–21.9)	21.0 (19.0–23.3)	8.6 (7.2–10.1)	9.5 (8.0–11.2)	1.1 (0.7–1.8)	1.6 (1.0–2.4)
At least 6	600	591	21.5 (18.3–25.0)	25.2 (21.8–28.9)	10.2 (7.9–12.9)	11.3 (8.9–14.2)	1.2 (0.5–2.4)	1.4 (0.6–2.6)

RZV = participants receiving the adjuvanted herpes zoster subunit vaccine; Placebo = participants receiving placebo; ZOE-50/70 = RZV efficacy studies in adults ≥50 YOA (NCT01165177) and ≥70 YOA (NCT01165229), respectively; % = percentage of participants in the category; CI = confidence interval; pIMDs = potential immune-mediated diseases; SAEs = serious adverse events; TVC = total vaccinated cohort.

^#Other than asthma.