Efficacy and safety of casirivimab-imdevimab combination on COVID-19 patients: A systematic review and meta-analysis randomized controlled trial
Imam Adi Wicaksono, Cecep Suhandi, Khaled M Elamin, Nasrul Wathoni
Heliyon, doi:10.1016/j.heliyon.2023.e22839
Background: The advantages and disadvantages of casirivimab-imdevimab for coronavirus disease 2019 are not well understood. We conducted a systematic review and meta-analysis of relevant literature to determine the therapeutic effectiveness and potential side effects of casirivimab-imdevimab in COVID-19 patients. Methods: Databases were searched from the time of their commencement until February 28 th , 2023. The primary results evaluated were the death rate at 28 days, progression of current clinical symptoms within 28 days, viral load, discharge from hospital, and any adverse events. Also, we contrasted the effects of the casirivimab-imdevimab treatment with placebo or standard of care. The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023412835). Results: A total of eight studies were included, comprising 19,819 patients, and conducted a qualitative assessment of their risk of bias using the Cochrane risk of bias tool. Casirivimabimdevimab effectively reduced the mortality rate (OR = 0.62; 95% CI of 0.40-0.98; p = 0.04; I 2 = 30%) and reduced the progression of clinical symptoms (OR = 0.86; 95% CI of 0.79-0.93; p = 0.0003; I 2 = 57%). Casirivimab-imdevimab also improved viral load clearance and hospital discharge. Additionally, the trials' findings demonstrated a slight decrease in the likelihood of adverse events occurring with the use of casirivimab-imdevimab.
Conclusion: Our research suggests that casirivimab-imdevimab may be a valuable, safe, and effective anti-SARS-CoV-2 regimen.
Consent for publication Not applicable.
Competing interests All authors declare no conflict of interest.
Ethics approval and consent to participate Ethical approval was not needed because this is a meta-analysis.
Authors' contribution IAW and CS: conceptualization; CS: methodology and software; IAW, KME, and NW: validation; IAW, CS, and NW: formal analysis; KME and NW: investigation; CS: writingoriginal draft preparation; IAW, KME, and NW: review and editing; and IAW: project administration and funding acquisition. All authors have read and agreed to the published version of the manuscript.
Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J o u r n a l P r e -p r o o f
References
Abani, Abbas, Abbas, Abbas, Abbasi et al., Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, The Lancet,
doi:10.1016/S0140-6736(22)00163-5Angamo, Mohammed, Peterson, Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis, Infection,
doi:10.1007/s15010-021-01671-0Benaicha, Khenhrani, Veer, Devi, Shahbaz et al., Efficacy of Molnupiravir for the Treatment of Mild or Moderate COVID-19 in Adults: A Meta-Analysis, Cureus,
doi:10.7759/cureus.38586Bhattacharya, Chatterjee, Sharma, Lee, Chakraborty, Delta variant (B.1.617.2) of SARS-CoV-2: current understanding of infection, transmission, immune escape, and mutational landscape, Folia Microbiol (Praha),
doi:10.1007/s12223-022-01001-3Chen, Liang, Wu, Li, Wang et al., Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection, J Pharm Anal,
doi:10.1016/j.jpha.2022.10.005Deng, Heybati, Ramaraju, Zhou, Rayner et al., Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis, Infection,
doi:10.1007/s15010-022-01825-8Ghazanfar, Haider, Gurjar, Hernandez, Jyala et al., Outcomes of Monoclonal Antibody Infusion Treatment During Delta (B.1.617.2and Omicron (B.1.1.529) COVID 19 Variant Surges among Vaccinated and Unvaccinated Patients, Health Serv Insights,
doi:10.1177/11786329221127153.JournalPre-proofHaddad, Dokmak, Karaman, A Comprehensive Review on the Efficacy of Several Pharmacologic Agents for the Treatment of COVID-19, Life,
doi:10.3390/life12111758Hansen, Baum, Pascal, Russo, Giordano et al., Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail, Science,
doi:10.1126/science.abd0827Herman, O'brien, Forleo-Neto, Sarkar, Isa et al., Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial, Lancet Infect Dis,
doi:10.1016/S1473-3099(22)00416-9Hernandez, Piscoya, Pasupuleti, Phan, Julakanti et al., Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis, American Journal of Medicine,
doi:10.1016/j.amjmed.2022.06.019Higgins, Altman, Gøtzsche, Jüni, Moher et al., The Cochrane Collaboration's tool for assessing J o u r n a l P r e -p r o o f risk of bias in randomised trials, BMJ (Online),
doi:10.1136/bmj.d5928Higgins, Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0
Huang, Mccreary, Bariola, Minnier, Wadas et al., Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2022.20957Isa, Forleo-Neto, Meyer, Zheng, Rasmussen et al., Repeat subcutaneous administration of casirivimab and imdevimab in adults is well-tolerated and prevents the occurrence of J o u r n a l P r e -p r o o f COVID-19, International Journal of Infectious Diseases,
doi:10.1016/j.ijid.2022.06.045Jovanoski, Kuznik, Becker, Hussein, Briggs, Cost-effectiveness of casirivimab/imdevimab in patients with COVID-19 in the ambulatory setting, J Manag Care Spec Pharm,
doi:10.18553/JMCP.2022.21469Kim, Yoo, Bae, Kim, Lee, Effectiveness of Paxlovid, an Oral Antiviral Drug, Against the Omicron BA.5 Variant in Korea: Severe Progression and Death Between July and November 2022, J Korean Med Sci,
doi:10.3346/jkms.2023.38.e211Kokic, Hillen, Tegunov, Dienemann, Seitz et al., Mechanism of SARS-CoV-2 polymerase stalling by remdesivir, Nat Commun,
doi:10.1038/s41467-020-20542-0Lin, Hung, Lai, Wang, Chen, The impact of neutralizing monoclonal antibodies on the outcomes of COVID-19 outpatients: A systematic review and meta-analysis of randomized controlled trials, J Med Virol,
doi:10.1002/jmv.27623Miranda, Mckinzie, Dobrovolsky, Revollo, Evaluation of the mutagenic effects of Molnupiravir and N4-hydroxycytidine in bacterial and mammalian cells by HiFi sequencing, Environ Mol Mutagen,
doi:10.1002/em.22510.JournalPre-proofMoher, Shamseer, Clarke, Ghersi, Liberati et al., Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement, Revista Espanola de Nutricion Humana y Dietetica,
doi:10.1186/2046-4053-4-1Najjar-Debbiny, Gronich, Weber, Khoury, Amar et al., Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients, Clinical Infectious Diseases,
doi:10.1093/cid/ciac443O'brien, Forleo-Neto, Sarkar, Isa, Hou et al., Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2021.24939Panda, Singh, Moirangthem, Bahurupi, Saha et al., Antiviral combination clinically better than standard therapy in severe but not in non-severe covid-19, Clin Pharmacol,
doi:10.2147/CPAA.S325083.JournalPre-proofPontolillo, Ucciferri, Borrelli, Di Nicola, Vecchiet et al., Molnupiravir as an Early Treatment for COVID-19: A Real Life Study, Pathogens,
doi:10.3390/pathogens11101121Portal-Celhay, Forleo-Neto, Eagan, Musser, Davis et al., Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients with SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2022.25411Quiros-Roldan, Amadasi, Zanella, Antoni, Storti et al., Monoclonal antibodies against sars-cov-2: Current scenario and future perspectives, Pharmaceuticals,
doi:10.3390/ph14121272Razonable, Pawlowski, O'horo, Arndt, Arndt et al., Casirivimab-Imdevimab treatment is associated with reduced rates of hospitalization among high-risk patients with mild to moderate coronavirus disease-19, EClinicalMedicine,
doi:10.1016/j.eclinm.2021.101102Ruggeri, Signorini, Caravaggio, Casirivimab and imdevimab: Costeffectiveness analysis of the treatment based on monoclonal antibodies on outpatients with Covid-19, PLoS One,
doi:10.1371/journal.pone.0279022Somersan-Karakaya, Mylonakis, Menon, Wells, Ali et al., Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19, J Infect Dis,
doi:10.1093/infdis/jiac320Suhandi, Mohammed, Wilar, El-Rayyes, Wathoni, Effectiveness of Mesenchymal Stem Cell Secretome on Wound Healing: A Systematic Review and Meta-analysis, Tissue Eng Regen Med,
doi:10.1007/s13770-023-00570-9Tian, Feng, Chen, Efficacy and Safety of Molnupiravir Treatment for COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2023.106870Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19, New England Journal of Medicine,
doi:10.1056/nejmoa2035002Weinreich, Sivapalasingam, Norton, Ali, Gao et al., e -p r o o f REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19, New England Journal of Medicine,
doi:10.1056/nejmoa2108163Zhuang, Xu, Wu, Yang, Lin et al., Postmarketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System, Br J Clin Pharmacol,
doi:10.1111/bcp.15783
