Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Sources and Searches
2.2. Eligibility Criteria
2.3. Data Extraction and Quality Assessment
2.4. Data Synthesis and Analysis
2.5. Subgroup Analyses
3. Results
3.1. Characteristics of the Identified Studies
3.2. Influenza Vaccine Characteristics and Vaccination Strategy
3.3. Vaccination Immunogenicity in the Identified Studies
3.4. Double Simultaneous Dose Influenza Vaccine
3.5. Booster-Dose Influenza Vaccine
3.6. Meta-Analysis of Vaccine Efficacy
3.6.1. Immunogenicity
3.6.2. Subgroup Analyses of Immunogenicity
3.7. Safety
4. Discussion
Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Conflicts of Interest
References
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Author Year | Design (Country) | Duration (Strains *) | Population | Case (Mean Age) | Vaccine Doseage | Time to Vaccine | Follow up (Quality *) |
---|---|---|---|---|---|---|---|
Giaquinta 2015 [11] (NCT01525004) | DB, Phase I RCT, (US) | 2011–2012 (A/H3N2) | Pediatric SOTR (kidney, liver, heart, lungs, intestine) | 38 (12.8) | HD (60μg HA) | Post-transplant for 6 months | 4 weeks (7) |
McManus 2014 [15] (NCT01216332) | DB, Phase I RCT, (US) | 2010–2011 (A/H3N2) 2011–2012 (A/H3N2) | Pediatric patients with Acute lymphocytic leukemia | 50 (8.5) | HD (60μg HA) | Under C/T for 1 month | 4 weeks (6) |
Halasa 2016 [13] (NCT01215734) | DB, Phase I, RCT (US) | 2010–201 1(A/H3N2) 2011–2012 (A/H3N2) | Adult Stem Cell Hematopoietic Transplant Recipients | 44 (50.0) | HD (60μg HA) | Post-transplant for 6 months | 4 weeks (7) |
Hakim 2016 [12] (NCT01205581) | OP, Phase II, RCT (US) | 2010–2011 (A/H3N2) 2011–2012 (A/H3N2) | Children with Cancer | 44 (11.3) | HD (60μg HA) | Under C/T or received C/T in the past 3 months | 3 weeks (5) |
Jamshed 2016 [14] (NCT01666782) | DB, Phase II, RCT (US) | 2012–2013 (A/H3N2) 2013–2014 (A/H1N1) | Adult with Cancer | 105 (53.4) | HD (60μg HA) | First day of chemotherapy | 4 weeks (6) |
Cordero 2017 [10] (EudraCT 2011-003243-21) | OP, Phase III, RCT (Spanish) | 2012–2013 (A/H3N2) | Adult SOTR (kidney, liver, heart, lungs) | 499 (55.9) | Booster (30μg HA) | Post-transplant for 1 month | 10 weeks (5) |
Natori 2018 [7] (NCT03139565) | DB, Phase III, RCT (Canada) | 2016–2017 (A/H3N2) | Adult SOTR (kidney, liver, heart, lung and pancreas) | 161 (57) | HD (60μg HA) | Post-transplant for 3 months | 4 weeks (6) |
Mombelli 2018 [16] (NCT02746783) | OP, Phase II, RCT (Switzerland) | 2014–2015 (A/H3N2) | Adult SOTR (kidney, liver) | 79 (58.6) | DD (30μg HA) | Post-transplant for 3 months | 4 weeks (5) |
Outcome Assessment | H1N1 | H3N2 | B | ||||||
---|---|---|---|---|---|---|---|---|---|
Number Trials (Patients) | Risk Difference (95% CI) | I2 (%) p-Value | Number Trials (Patients) | Risk Ratio (95% CI) | I2 (%) p-Value | Number Trials (Patients) | Risk Ratio (95% CI) | I2 (%) p-Value | |
SeroConversion | 8 (921) | 0.1278 (0.0347; 0.2208) | 48.7% 0.0071 * | 8 (921) | 0.1000 (-0.0140; 0.2141) | 65.7% 0.0856 | 8 (921) | −0.0004 (−0.0999; 0.0991) | 63.7% 0.9938 |
Double does (30 µg) | 2 (503) | 0.0483 (−0.0195; 0.1161) | 0.0% 0.1625 | 2 (503) | 0.0327 (−0.0374; 0.1028) | 0.0% 0.3603 | 2 (503) | 0.0424 (−0.0301; 0.1149) | 0.0% 0.2514 |
High does (60 µg) | 6 (418) | 0.1801 (0.0651; 0.2952) | 31.8% 0.0021 * | 6 (418) | 0.1300 (−0.0349; 0.2950) | 66.9% 0.1223 | 6 (418) | −0.0225 (−0.1865; 0.1416) | 73.6% 0.7883 |
Mean Age > 18 | 5 (804) | 0.1236 (0.0310; 0.2162) | 44.4% 0.0088 * | 5 (804) | 0.1164 (0.0088; 0.2240) | 56.3% 0.0340 * | 5 (804) | −0.0043 (−0.1406; 0.1319) | 76.3% 0.9503 |
Mean Age < 18 | 3 (117) | 0.1094 (−0.1916; 0.4105) | 68.6% 0.4760 | 3 (117) | 0.0548 (−0.3253; 0.4349) | 82.0% 0.7776 | 3 (117) | 0.0182 (−0.1292; 0.1657) | 20.4% 0.8083 |
Chemotherapy | 3 (180) | 0.1386 (−0.1294; 0.4066) | 72.3% 0.3107 | 3 (180) | 0.0044 (−0.2737; 0.2825) | 74.3% 0.9754 | 3 (180) | 0.1098 (0.0080; 0.2115) | 0.0% 0.0344 * |
Post−transplant | 5 (739) | 0.0920 (0.0226; 0.1615) | 11.0% 0.0093 * | 5 (739) | 0.1392 (0.0021; 0.2763) | 67.9% 0.0466 * | 5 (739) | −0.0608 (−0.1972; 0.0756) | 70.2% 0.3821 |
SeroProtection | 8 (921) | 0.0713 (0.0209; 0.1217) | 0.0% 0.0056 * | 8 (921) | 0.0638 (−0.0092; 0.1368) | 50.2% 0.0868 | 8 (921) | 0.0709 (−0.0230; 0.1647) | 64.1% 0.1388 |
Double does (30 µg) | 2 (503) | 0.1212 (0.0404; 0.2020) | 0.0% 0.0033 * | 2 (503) | 0.0976 (0.0268; 0.1684) | 0.0% 0.0068 * | 2 (503) | 0.0961 (0.0309; 0.1613) | 0.0% 0.0038 * |
High does (60 µg) | 6 (418) | 0.0395 (−0.0250; 0.1040) | 0.0% 0.2303 | 6 (418) | 0.0505 (−0.0571; 0.1581) | 53.9% 0.3579 | 6 (418) | 0.0514 (−0.1139; 0.2168) | 72.2% 0.5420 |
Mean Age > 18 | 5 (804) | 0.0767 (0.0224; 0.1309) | 0.0% 0.0056 * | 5 (804) | 0.0903 (−0.0025; 0.1832) | 68.3% 0.0565 | 5 (804) | 0.1094 (0.0090; 0.2099) | 69.8% 0.0327 * |
Mean Age < 18 | 3 (117) | 0.0374 (−0.0987; 0.1735) | 0.0% 0.5898 | 3 (117) | −0.0200 (−0.1580; 0.1180) | 0.0% 0.7767 | 3 (117) | −0.0677 (−0.2800; 0.1445) | 37.5% 0.5317 |
Chemotherapy | 3 (180) | 0.0365 (−0.0496; 0.1227) | 0.0% 0.4061 | 3 (180) | −0.0101 (−0.0798; 0.0596) | 0.0% 0.7759 | 3 (180) | 0.0788 (−0.2991; 0.4568) | 86.6% 0.6827 |
Post-transplant | 5 (739) | 0.0894 (0.0272; 0.1515) | 0.0% 0.0048 * | 5 (739) | 0.1084 (0.0272; 0.1897) | 36.9% 0.0089 * | 5 (739) | 0.0672 (0.0175; 0.1170) | 0.0% 0.0080 * |
Outcome Assessment | Number of Trials (Patients) | Risk Ratio (95% CI) Fixed-Effect Estimate | Risk Ratio (95% CI) Random-Effect | p-Value Random-Effect | Heterogeneity I2 (%) |
---|---|---|---|---|---|
Adverse Events, all | 8 (1007) | 0.8879 (0.8072; 0.9766) | 1.0211 (0.6770; 1.5401) | 0.9208 | 93.7% |
Mild | 6 (792) | 0.8094 (0.7120; 0.9201) | 0.8698 (0.5722; 1.3221) | 0.5137 | 88.7% |
Moderate | 6 (792) | 0.9003 (0.7546; 1.0741) | 0.9626 (0.5165; 1.7940) | 0.9044 | 91.5% |
Severe | 6 (792) | 1.0360 (0.7095; 1.5129) | 1.1472 (0.4112; 3.2007) | 0.7931 | 75.6% |
Serious | 5 (656) | 0.8787 (0.5823; 1.3259) | 0.8228 (0.5514; 1.2276) | 0.3394 | 0.0% |
Rejection | 3 (787) | 1.3454 (0.4205; 4.3054) | 1.3795 (0.3858; 4.9330) | 0.6207 | 0.0% |
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Lai, J.-J.; Lin, C.; Ho, C.-L.; Chen, P.-H.; Lee, C.-H. Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials. J. Clin. Med. 2019, 8, 590. https://doi.org/10.3390/jcm8050590
Lai J-J, Lin C, Ho C-L, Chen P-H, Lee C-H. Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials. Journal of Clinical Medicine. 2019; 8(5):590. https://doi.org/10.3390/jcm8050590
Chicago/Turabian StyleLai, Jiun-Ji, Chin Lin, Ching-Liang Ho, Po-Huang Chen, and Cho-Hao Lee. 2019. "Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials" Journal of Clinical Medicine 8, no. 5: 590. https://doi.org/10.3390/jcm8050590
APA StyleLai, J. -J., Lin, C., Ho, C. -L., Chen, P. -H., & Lee, C. -H. (2019). Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials. Journal of Clinical Medicine, 8(5), 590. https://doi.org/10.3390/jcm8050590