3. Adverse events: adjuvanted recombinant varicella zoster virus subunit zoster vaccine (RZV).
| Comparison (studies) | Results |
| RZV versus placebo (Cunningham 2016; Lal 2015) | The adverse events related to RZV versus placebo were:
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RZV: lower or higher quantities of adjuvants plus gE subunit VZV versus unadjuvanted gE or saline (Chlibek 2013) |
The incidence of adverse events in participants randomised to 4 different groups was compared as follows:
We compared each of the groups with all of the other groups (total of 6 comparisons) as follows: 50 μg gE/AS01E versus 50 μg gE/AS01B There was a significantly higher incidence of adverse events in participants who received a higher quantity of adjuvant (AS01B):
There were no significant differences between groups for all other adverse events: any grade 3 symptom, any general symptom, any general grade 3 symptom, grade 3 fatigue, fever, gastrointestinal symptoms, grade 3 gastrointestinal symptoms, grade 3 headache, myalgia, grade 3 myalgia, any grade 3 local symptom, local grade 3 pain, local grade 3 redness, local swelling and local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 50 μg gE/AS01E versus 50 μg gE/saline (unadjuvanted)
All these differences in incidence of adverse events favoured the unadjuvanted gE group. There were no significant differences between groups for the following adverse events: any grade 3 symptom, any general grade 3 symptom, fatigue, grade 3 fatigue, gastrointestinal symptoms, grade 3 gastrointestinal symptoms, headache, grade 3 myalgia, any local grade 3 symptom, local grade 3 pain, local grade 3 redness and local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever or grade 3 headache in either group. 50 μg gE/AS01B versus 50 μg gE/saline (unadjuvanted)
All these differences in incidence of adverse events favoured unadjuvanted gE. There were no significant differences between groups for the following adverse events: any grade 3 symptom, any general grade 3 symptom, grade 3 fatigue, gastrointestinal symptoms, grade 3 headache, grade 3 myalgia, any local grade 3 symptom, local grade 3 pain, local grade 3 redness and local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever or grade 3 gastrointestinal symptoms in either group. 50 μg gE/AS01E versus saline
All these differences in incidence of adverse events favoured the saline group. There were no significant differences between groups for the following adverse events: any grade 3 symptom, any general grade 3 symptom, fatigue, grade 3 fatigue, fever, gastrointestinal symptoms, grade 3 gastrointestinal symptoms, headache, grade 3 headache, grade 3 myalgia, any local grade 3 symptom, local grade 3 pain, local redness, local grade 3 redness, local swelling and local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever or grade 3 headache in either group. 50 μg gE/AS01B versus saline
All these differences in incidence of adverse events favoured the saline group. There were no significant differences between groups for the following adverse events: any grade 3 symptom, any general grade 3 symptom, grade 3 fatigue, fever, gastrointestinal symptoms, grade 3 gastrointestinal symptoms, grade 3 headache, grade 3 myalgia, any local grade 3 symptom, local grade 3 pain, local grade 3 redness, local swelling and local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 50 μg gE/saline (unadjuvanted) versus saline
There were no significant differences between groups for the following adverse events: any grade 3 symptom, any general symptom, any general grade 3 symptom, fatigue, grade 3 fatigue, fever, gastrointestinal symptoms, grade 3 gastrointestinal symptoms, headache, myalgia, grade 3 myalgia, any local symptom, local pain, local redness and local swelling, or consent withdrawal. No participants in either group had grade 3 fever, grade 3 headache, any local grade 3 symptom, local grade 3 pain, local grade 3 redness, local grade 3 swelling, loss to follow‐up, and serious adverse events. |
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RZV: 3 groups of VZV subunit gE in 3 different quantities versus unadjuvanted gE or saline (Chlibek 2014) |
The incidence of adverse events in participants randomised to 5 different groups was compared as follows:
We compared each of the groups to all other groups (total of 10 comparisons) as follow: 25 µg gE/AS01B versus 50 µg gE/AS01B There were no differences between groups in the incidence of the following adverse events: any fatigue, grade 3 fatigue, any fever, grade 3 fever, any headache, grade 3 headache, any myalgia, grade 3 myalgia, local pain, local grade 3 pain, local redness, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. 25 µg gE/AS01B versus 100 µg gE/AS01B There were no differences between groups in the incidence of the following adverse events: any fatigue, grade 3 fatigue, any fever, any headache, grade 3 headache, any myalgia, grade 3 myalgia, local pain, grade 3 local pain, local redness, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. 50 µg gE/AS01B versus 100 µg gE/AS01B
There were no differences between groups in the incidence of other adverse events: any fatigue, grade 3 fatigue, any fever, grade 3 fever, any headache, grade 3 headache, grade 3 myalgia, local pain, local grade 3 pain, local redness, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, and serious adverse events. 25 µg gE/AS01B versus 100 µg gE/saline (unadjuvanted gE)
All these differences in incidence of adverse events favoured unadjuvanted gE. There were no differences in the incidence of the following adverse events: grade 3 fatigue, any fever, any headache, grade 3 headache, grade 3 myalgia, local grade 3 pain, local grade 3 redness, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 50 µg gE/AS01B versus 100 µg gE/saline (unadjuvanted gE)
All these differences in incidence of adverse events favoured unadjuvanted gE. There were no differences in the incidence of the following adverse events: grade 3 fatigue, any fever, grade 3 headache, grade 3 myalgia, local grade 3 pain, local grade 3 redness, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 100 µg gE/AS01B versus 100 µg gE/saline (unadjuvanted gE)
All these differences in incidence of adverse events favoured unadjuvanted gE. There were no differences in the incidence of the following adverse events: grade 3 fatigue, any fever, grade 3 headache, grade 3 myalgia, local grade 3 pain, local grade 3 redness, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 25 µg gE/AS01B versus saline + 100 µg gE/AS01B
All differences in incidence of adverse events favoured saline + 100 µg gE/AS01B. There were no differences in the incidence of the following adverse events: any fatigue, grade 3 fever, any headache, grade 3 headache, grade 3 myalgia, local grade 3 pain, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. 50 µg gE/AS01B versus saline + 100 µg gE/AS01B
All differences in incidence of adverse events favoured saline + 100 µg gE/AS01B. There were no differences in the incidence of the following adverse events: grade 3 fatigue, any fever, grade 3 fever, grade 3 headache, grade 3 myalgia, local grade 3 pain, local redness, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. 100 µg gE/AS01B versus saline + 100 µg gE/AS01B
All differences in incidence of adverse events favoured saline + 100 µg gE/AS01B. There were no differences in the incidence of the following adverse events: grade 3 fatigue, headache, grade 3 headache, grade 3 myalgia, local grade 3 pain, local grade 3 redness, local swelling, local grade 3 swelling, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever in either group. Saline + 100 µg gE/AS01B versus 100 µg gE/saline (unadjuvanted gE)
All differences in incidence of adverse events favoured 100 µg gE/saline. There were no differences in the incidence of the following adverse events: any fatigue, grade 3 fatigue, any fever, any headache, any myalgia, grade 3 myalgia, local grade 3 pain, local grade 3 redness, consent withdrawal, loss to follow‐up, and serious adverse events. No participants had grade 3 fever, grade 3 headache, or local grade 3 swelling in either group. |
| RZV: 2 doses given at 3 different intervals (Lal 2018) | There were no statistically significant differences between groups for any of the 3 comparisons (RZV 2 doses 2 months apart versus RZV 2 doses 6 months apart; RZV 2 doses 2 months apart versus RZV 2 doses 12 months apart; and RZV 2 doses 6 months apart versus RZV 2 doses 12 months apart) in incidence of the following adverse events: at least 1 unsolicited AE symptom, at least 1 unsolicited AE symptom related to vaccination. There were no significant differences between groups for the following general symptoms: fatigue, grade 3 fatigue, fever, grade 3 fever, headache, grade 3 headache, myalgia, grade 3 myalgia, gastrointestinal symptom, grade 3 gastrointestinal symptom. The average duration of solicited general symptoms was ≤ 2 days. There were no significant differences between groups for the following local symptoms: local pain, grade 3 local pain, local redness, grade 3 redness, local swelling, grade 3 local swelling. The average duration of local symptoms was ≤ 3 days. There were no significant differences between groups for the following: SAE, withdrawn due to an SAE, consent withdrawal, lost to follow‐up. There were no cases of suspected zoster or autoimmune disease throughout the study in any of the groups. |
| RZV IM route versus RZV SC route (Vink 2017) | There was a significant difference between groups favouring the IM route for the following adverse events: injection site redness (RR 1.73, 95% CI 1.18 to 2.55; RD 0.37, 95% CI 0.15 to 0.58; NNTH 2.7, 95% CI 1.7 to 6.7); injection site swelling (RR 2.00, 95% CI 1.25 to 3.21; RD 0.40, 95% CI 0.17 to 0.63; NNTH 2.5, 95% CI 1.6 to 5.9); grade 3 injection site swelling (RR 5.00, 95% CI 1.19 to 20.92; RD 0.27, 95% CI 0.08 to 0.46; NNTH 3.7, 95% CI 2.2 to 12.5); injection site pruritus (RR 2.10, 95% CI 1.20 to 3.67; RD 0.37, 95% CI 0.13 to 0.60; NNTH 2.7, 95% CI 1.7 to 7.7). There were no differences between groups for all other adverse events. There were no deaths or autoimmune diseases. |
| RZV versus pneumo‐23 (Maréchal 2018) |
Serious adverse events within 30 days after vaccination
There were no serious adverse events or pIMDs that were considered vaccine‐related. Serious adverse events from 30 days after last vaccination up to the end of study
There were no serious adverse events or pIMDs that were considered vaccine‐related. When comparing the group that received RZV + pneumo‐23 versus the group that received only pneumo‐23, the following systemic adverse events occurred within 7 days after vaccination:
Injection site AE
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| RZV + TDaPV co‐administration group versus RZV + TDaPV not co‐administration group (NCT02052596) | There were no significant differences between groups for the following: death, serious adverse events, systemic adverse events, injection site adverse events, unsolicited vaccine‐related adverse events. There were no pIMDs. |
| RZV + IIV4 co‐administration group versus not co‐administration group (Schwarz 2017) | There were no deaths. There were no significant differences between groups except for the following AEs:
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AE: adverse event or adverse experiences AS01: liposome‐based adjuvant system containing the immunoenhancers 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and the saponin QS‐21 (Quillaja saponaria Molina, fraction 21) Adjuvanted gE/AS01B: 50 μg purified gE with adjuvant B (1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21) Adjuvanted gE/AS01E: 50 μg purified gE with adjuvant E (500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21) AS01B: adjuvant B composed of 1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21 AS01E: adjuvant E composed of 500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21 CI: confidence interval Elderly or older adults: aged ≥ 60 years old gE: recombinant subunit VZV composed of glycoprotein E gE/saline: unadjuvanted gE ID: identification IIV4: inactivated quadrivalent influenza vaccines IM: intramuscular MPL: immunoenhancer 3‐O‐desacyl‐4′‐monophosphoryl lipid A NNTB: number needed to treat for an additional beneficial outcome NNTH: number needed to treat for an additional harmful outcome pIMDs: potential immune‐mediated diseases pneumo‐23 vaccine: 23–valent pneumococcal polysaccharide vaccine QS‐21: immunoenhancer saponin Quillaja saponaria Molina, fraction 21 RD: risk difference RR: risk ratio RZV: adjuvanted recombinant zoster vaccine (contains 50 µg of recombinant VZV glycoprotein E, and the liposome‐based AS01B adjuvant system contains 50 µg of 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and 50 µg of Quillaja saponaria Molina, fraction 21 (QS21)) SAEs: serious adverse events SC: subcutaneously or subcutaneous TDaPV: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine VZV: varicella zoster virus