Preliminary Evidence of Good Safety Profile and Outcomes of Early Treatment With Tixagevimab/Cilgavimab Compared to Previously Employed Monoclonal Antibodies for COVID-19 in Immunocompromised Patients
MD. Andrea Lombardi, Giulia Viero, Simone Villa, Simona Biscarini, Emanuele Palomba, Cecilia Azzara', Nathalie Iannotti, Bianca Mariani, Camilla Genovese, Mara Tomasello, Anna Tonizzo, Marco Fava, Antonia Grazia Valzano, Letizia Morlacchi, Maria Francesca Donato, Giuseppe Castellano, Ramona Cassin, Maria Carrabba, Antonio Muscatello, Andrea Gori, Alessandra Bandera
doi:10.20944/preprints202301.0359.v1
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Authors contributions AL, SV, AG, and AB conceived the study. GV, SB, EP, CA, NI, BM, CG, MT, AT, MF, AGV, LCM, FD, GC, RC, MC and AM enrolled the patients and collected clinical data. AL and SV performed the statistical analysis. AL, GV and SV wrote the first draft of the manuscript. All the other authors reviewed the final version of the manuscript.
Conflict of interests AL Gilead Sciences Inc. and Insmed Italia. AB Quiagen, Pfizer, Nordic Pharma, ViiV, SOBI, and Gilead Sciences. FD Kedrion, Gilead Sciences, Biotest, and Novartis. AM Gilead Sciences, Menarini, and Nordic Pharma. SB Infectopharma. MC Takeda and Kedrion. All the other authors have nothing to declare.
References
Aifa, AIFA Evusheld trattamento 2022
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doi:10.3390/biomedicines10082002Ecdc, ECDC VOCs monitoring
Holland, Ginde, Paredes, Murray, Engen et al., Tixagevimabcilgavimab for treatment of patients hospitalised with COVID-19: a randomised, doubleblind, phase 3 trial, Lancet Respir Med,
doi:10.1016/S2213-2600(22)00215-6Jurdi, Morena, Cote, Bethea, Azzi et al., Tixagevimab/cilgavimab preexposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave, Am J Transplant,
doi:10.1111/ajt.17128Levin, Ustianowski, Wit, Launay, Avila et al., Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2116620Loo, Mctamney, Arends, Abram, Aksyuk et al., The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans, Sci Transl Med,
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doi:10.1038/s41598-022-22431-6Montgomery, Hobbs, Padilla, Arbetter, Templeton et al., Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial, Lancet Respir Med,
doi:10.1016/S2213-2600(22)00180-1Nguyen, Flahault, Chavarot, Melenotte, Cheminant et al., Preexposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients, Clin Microbiol Infect,
doi:10.1016/j.cmi.2022.07.015DOI record:
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"abstract": "<jats:p>Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalization and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson&rsquo;s chi-square or Fisher&rsquo;s exact test for categorical variables, whereas the Wilcoxon rank&ndash;sum test was employed for continuous ones. Kaplan&ndash;Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups in terms of clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p=0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL shows favourable outcomes in a small group of immunocompromised patients, reporting no significant difference when compared to similar patients treated with other mAbs.</jats:p>",
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