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欧洲EPICOVIDEHA注册中心的一项配对分析:高危血液恶性肿瘤患者COVID-19治疗中,MOLNUPIRAVIR与NIRMATRELVIR/RITONAVIR的比较。

MOLNUPIRAVIR COMPARED TO NIRMATRELVIR/RITONAVIR FOR COVID-19 IN HIGH-RISK PATIENTS WITH HAEMATOLOGICAL MALIGNANCY IN EUROPE. A MATCHED-PAIRED ANALYSIS FROM THE EPICOVIDEHA REGISTRY.

发表日期:2023 Aug 13
作者: Jon Salmanton-García, Francesco Marchesi, Philipp Koehler, Barbora Weinbergerová, Natasa Čolović, Iker Falces-Romero, Caterina Buquicchio, Francesca Farina, Jens VAN Praet, Monika M Biernat, Federico Itri, Lucia Prezioso, Carlo Tascini, Antonio Vena, Alessandra Romano, Mario Delia, Julio Dávila-Valls, Sonia Martín-Pérez, Esperanza Lavilla-Rubira, Tatjana Adžić-Vukičević, Daniel García-Bordallo, Alberto López-García, Mariana Criscuolo, Verena Petzer, Nicola S Fracchiolla, Ildefonso Espigado, Uluhan Sili, Stef Meers, Nurettin Erben, Chiara Cattaneo, Athanasios Tragiannidis, Eleni Gavriilaki, Martin Schönlein, Mirjana Mitrovic, Nikola Pantic, Maria Merelli, Jorge Labrador, José-Ángel Hernández-Rivas, Andreas Glenthøj, Guillemette Fouquet, Maria Ilaria Del Principe, Michelina Dargenio, María Calbacho, Caroline Besson, Milena Kohn, Stefanie Gräfe, Ditte Stampe Hersby, Elena Arellano, Gökçe MelisÇOLAK, Dominik Wolf, Monia Marchetti, Anna Nordlander, Ola Blennow, Raul Cordoba, Bojana Mišković, Miloš Mladenović, Martina Bavastro, Alessandro Limongelli, Laman Rahimli, Livio Pagano, Oliver A Cornely
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

莫卢尼匹拉韦和尼马替尔维/利托那韦是抗病毒药物,用于防止SARS-CoV-2感染的严重程度进展,可以降低住院和死亡率。尼马替尔维/利托那韦于2021年12月在欧洲获得授权,而莫卢尼匹拉韦截至2022年2月尚未在欧洲获得许可。莫卢尼匹拉韦可能是尼马替尔维/利托那韦的替代品,因为它显示出较少的药物相互作用和禁忌症。与莫卢尼匹拉韦相关的一个注意事项是其诱导病毒突变的作用方式。在未患血液恶性肿瘤的患者临床试验中,莫卢尼匹拉韦的死亡率降低程度较尼马替尔维/利托那韦要小。关于这两种药物在高危重型COVID-19患者中的比较疗效了解甚少。因此,在我们的血液恶性肿瘤患者队列中,我们评估了莫卢尼匹拉韦与尼马替尔维/利托那韦的疗效。从EPICOVIDEHA登记处检索了接受莫卢尼匹拉韦或尼马替尔维/利托那韦单药治疗COVID-19的患者的临床数据。接受莫卢尼匹拉韦治疗的患者根据性别、年龄(±10岁)和基线血液恶性肿瘤严重程度与接受尼马替尔维/利托那韦治疗的对照组进行配对。共有116名接受莫卢尼匹拉韦治疗COVID-19的患者与接受尼马替尔维/利托那韦治疗的对照组相匹配。在两个组中,男性患者68人(59%);莫卢尼匹拉韦组中的中位年龄为64岁(IQR 53-74),尼马替尔维/利托那韦组中的中位年龄为64岁(IQR 54-73);在两个组中,有57%(n=66)的患者的基线血液恶性肿瘤受控制,13%(n=15)稳定,30%(n=35)在COVID-19发病时有活动性疾病。在COVID-19感染期间,三分之一的患者从两个组中入院。尽管两组接种疫苗的比例相似(莫卢尼匹拉韦 n=77, 66% vs 尼马替尔维/利托那韦 n=87, 75%),接受尼马替尔维/利托那韦治疗的患者多次接种疫苗的比例较高(n=27, 23%)而接受莫卢尼匹拉韦治疗的患者较少(n=5, 4%,p<0.001)。在COVID-19严重程度(p=0.39)或住院率(p=1.0)方面未发现差异。在总体死亡率(p=0.78)和生存概率(d30 p=0.19,d60 p=0.67,d90 p=0.68,随访最后一天 p=0.68)方面也未发现统计学上的显著差异。在所有患者中,死亡原因要么归因于COVID-19,要么按照主治医生的判断,COVID-19感染是导致死亡的原因之一。在血液恶性肿瘤患者和COVID-19的高风险患者中,莫卢尼匹拉韦在此配对分析中显示出与尼马替尔维/利托那韦相当的住院和死亡率。莫卢尼匹拉韦似乎是血液恶性肿瘤患者COVID-19治疗的一个可行替代方案。版权所有 © 2023. Elsevier Ltd 公布。
Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections, which reduce both hospitalization and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, while molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir, because it displays less frequent drug-drug interactions and contraindications. A caveat connected to molnupiravir derives from the mode of action inducing viral mutations. In clinical trials on patients without haematological malignancy, mortality rate reduction of molnupiravir appeared less pronounced than that of nirmatrelvir/ritonavir. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, we here assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our cohort of patients with haematological malignancies.Clinical data of patients treated either with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and baseline haematological malignancy severity to controls treated with nirmatrelvir/ritonavir.A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (IQR 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 57% (n=66) of the patients had controlled baseline haematological malignancy, 13% (n=15) stable, and 30% (n=35) had active disease at COVID-19 onset in each of the groups. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=77, 66% vs nirmatrelvir/ritonavir n=87, 75%), those treated with nirmatrelvir/ritonavir had more often received four doses (n=27, 23%) as compared to patients treated with molnupiravir (n=5, 4%, p<0.001). No differences were detected in COVID-19 severity (p=0.39) or hospitalization (p=1.0). No statistically significant differences were identified in overall mortality rate (p=0.78) or in survival probability (d30 p=0.19, d60 p=0.67, d90 p=0.68, last day of follow up p=0.68). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death as per treating physician's judgement.In high-risk patients with haematological malignancies and COVID-19, molnupiravir showed rates of hospitalization and mortality comparable to those of nirmatrelvir/ritonavir in this matched-pair analysis. Molnupiravir appears to be a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.Copyright © 2023. Published by Elsevier Ltd.