Table 2.
Overview of real-world evidence investigating the incidence of selected adverse eventsa after administration of the recombinant zoster vaccine.
| Safety dataa |
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|---|---|---|---|---|---|
| Publication | Study type/period | Population | Sample | Outcome | Results |
| Adults aged ≥ 50 yearsb | |||||
| Hesse et al. MMWR Morb Mortal Wkly 201934 | Retrospective analysis of VAERS data Oct 2017−Jun 2018 |
US population | ~3.2 million RZV doses | Total reports of AEs, N (%) n per 100,000 doses distributed |
4381 (100.0) 136 |
| Serious AEs, n (%) | 130 (3.0) | ||||
| Fever, n (%) | 1034 (23.6) | ||||
| Injection-site pain, n (%) | 985 (22.5) | ||||
| Injection-site erythema, n (%) | 880 (20.1) | ||||
| Tavares-Da-Silva et al. Vaccine 20206 | Retrospective analysis of the GSK safety database Oct 2017−Feb 2019 |
Worldwide population | 9,323,118 RZV doses | Total reports of AEs, N (%) n per 100,000 doses distributed |
15,638 (100) 167.7 |
| Serious AEs, n (%) | 741 (4.7) | ||||
| Fever, n (%) | 1658 (10.6) | ||||
| Injection-site reactions, n (%) | 2849 (61.4) | ||||
| Injection-site pain, n (%) | 1699 (10.9) | ||||
| Nelson et al. Am J Epidemiol 202348 | Prospective analysis of VSD data Jan 2018−Dec 2019 |
US adults ≥ 50 years enrolled in 7 VSD-data-contributing healthcare systems | End-of-surveillance analysis: RZV recipients: n = 647,307 first and second doses; “well-visit” comparators:c n = 1,086,206 | Diagnoses consistent with systemic reactions: RZV group, n (rate per 10,000 dosesd) RZV vs “well-visit” group, aRRd (95% CI) |
2202 (31.49) 1.17 (1.10−1.24) |
| Diagnoses consistent with local reactions: RZV group, n (rate per 10,000 dosesd) RZV vs “well-visit” group, aRRd (95% CI) |
202 (2.69) 2.75 (2.14−3.54) |
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| Any adverse reaction diagnosis: RZV group, n (rate per 10,000 dosesd) RZV vs “well-visit” group, aRRd (95% CI) |
2497 (35.63) 1.27 (1.20−1.34) |
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| Urgent or emergency healthcare visit for any reason RZV group, n (rate per 10,000 dosesd) RZV vs “well-visit” group, aRRd (95% CI) |
2541 (36.93) 1.01 (0.96−1.07) |
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| Pirrotta et al. Drug Saf 202135 | Retrospective analysis of the GSK safety database Oct 2017−Apr 2020 |
Worldwide population | 32,597,779 RZV doses | Reports of AEs suggestive of HZ or HZ complications, n | 2423 |
| Reports of possible VZV reactivation,e n | 1928 | ||||
| Reports of vaccination failure, n | 645 | ||||
| Unique reports of AEs suggestive of other vesicular and bullous cutaneous eruptions (non-HZ), n | 810 | ||||
| Injection-site eruptions, n | 74 | ||||
| Non-injection-site eruptions, n | 557 | ||||
| Yih et al. Am J Epidemiol 202236 | Retrospective analysis of the IBM MarketScan database Jan 2018−May 2020 |
Commercially insured US adults aged ≥ 50 years | 1,014,329 RZV doses | ICD-10 Diagnosis Description (post-vaccination risk window detected): | Cases, n in 56-day follow-up; n in risk window (excess cases per 100,000 doses) |
| Dizziness and giddiness (days 1−8) | 1448; 251 (7.8) | ||||
| Poisoning by, adverse effect of, and underdosing of diuretics and other and unspecified drugs, medicaments, and biological substances (days 1−4)f | 187; 68 (5.9) | ||||
| Fever of other and unknown origin (days 1−2) | 973; 82 (5.1) | ||||
| Syncope and collapse (days 1−3) | |||||
| Fever, unspecified (days 1−2) | 908; 74 (4.5) | ||||
| Adverse effects of other vaccines and biological substances (days 1−3)f | 40; 33 (3.2) | ||||
| Yih et al. Am J Epidemiol 202347 | Retrospective analysis of the IBM MarketScan database Jan 2018−May 2020 |
Commercially insured US adults aged ≥ 50 years | 999,876 RZV doses | ICD-10 Diagnosis Descriptionf (days 1−28 post vaccination) |
Cases, n (attributable risk per 100,000 doses): |
| Adverse effect of other vaccines and biological substances | 37 (3.7) | ||||
| Other complications following immunization, not classified elsewhere | 27 (2.6) | ||||
| Poisoning by, adverse effect of, and underdosing of viral vaccines | 24 (2.4) | ||||
| Adverse effect of other viral vaccines | 23 (2.3) | ||||
| Ackerson et al. Vaccine 202137 | Retrospective cohort study Apr–Nov 2018 |
Kaiser Permanente Southern California members aged ≥ 50 years | 31,120 individuals who received at least one RZV dose: n = 10,222 first dose only n = 20,898 second dose completed |
Days 1−7 after first RZV dose: Medically attended local reactions First dose only group, n (%) Second dose completed group, n (%) |
21 (0.2) 32 (0.2) |
| Medically attended systemic reactions First dose only group, n (%) Second dose completed group, n (%) |
55 (0.5) 85 (0.4) |
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| Medically attended pain First dose only group, n (%) Second dose completed group, n (%) |
32 (0.3) 50 (0.2) |
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| Immunocompromised adults aged ≥ 18 years | |||||
| Baumrin et al. Blood Adv 202124 | Prospective cohort study Dec 2018−Jun 2020 |
Allogeneic hematopoietic cell transplantation recipients | 158 patients who received at least one RZV doseg | Days 1−7 after vaccination:h All solicited AEs Any grade, n/N (%) Grade 3, n/N (%) |
139/151 (92.1) 49/151 (32.5) |
| Injection-site AEs Any grade, n/N (%) Grade 3, n/N (%) |
131/150 (87.3) 28/150 (18.7) |
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| Pain Any grade, n/N (%) Grade 3, n/N (%) |
129/150 (86.0) 24/150 (16.0) |
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| Days 1−30 after vaccination:h All unsolicited AEs, n/N (%) Related to trial intervention, n/N (%) |
11/150 (7.3) 6/150 (4.0) |
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| Serious AEs, n/N (%) | 2/150 (1.3) | ||||
| Barghash et al. J Heart Lung Transplant 202038 | Retrospective cohort study Sep 2018−Jun 2020 |
Heart transplant recipients | 65 patients who received at least one RZV dose: n = 65 first dose n = 46 second dose |
All AEs After first dose, n (%) After second dose, n (%) |
23 (35.4) 13 (28.3) |
| Injection-site reactions After first dose, n (%) After second dose, n (%) |
19 (29.2) 13 (28.3) |
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| Fever After first dose, n (%) After second dose, n (%) |
1 (1.5) 1 (2.2) |
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| Gastrointestinal side effects After first dose, n (%) After second dose, n (%) |
1 (1.5) 0 (0) |
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| Headache After first dose, n (%) After second dose, n (%) |
1 (1.5) 0 (0) |
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aThe safety data listed for each study are not exhaustive; a selection of key outcomes is presented.
bThe vast majority of cases involved individuals aged ≥ 50 years, as this was the age group for which RZV was indicated at the time of the data collection. In some studies, nevertheless, a small fraction of cases came from individuals aged <50 years.
cIndividuals who had not received RZV, had an annual well-person healthcare visit during the RZV uptake period, and had been vaccinated against influenza during the year before their visit.
dPropensity-score –adjusted for age, sex, study site, a dermatology visit, an optometry visit, and prior zoster vaccine live vaccination.
eWhen considering an RF of 75%, the observed number of possible VZV reactivations was lower than the expected number in all countries. The observed number of possible VZV reactivations was higher than the expected number for RFs of <10% for worldwide and the USA, <56% for Canada, and <53% for Germany. The RF is the proportion of possible VZV reactivations reported among all those events that actually occurred in the vaccinated general population within the risk period, regardless of the causality.
fThe authors noted that previous studies examining similar nonspecific post-vaccination signals case by case using similar methodology found that the majority of the cases experienced conditions such as injection-site reactions, fever, fatigue, and headache.
gThe majority of the participants had co-administered vaccines (94% at first RZV dose, 84% at second RZV dose).
hThe data are reported as n/N. The total N varied, as participants with missing symptom diaries for the first or second RZV dose were removed unless a grade 3 event was reported.
AE, adverse event; aRR, adjusted relative risk; CI, confidence interval; HZ, herpes zoster; RF, reported fraction; RZV, recombinant zoster vaccine; US, United States; VAERS, Vaccine Adverse Event Reporting System; VSD, Vaccine Safety Datalink; VZV, varicella zoster virus.