TY - JOUR

T1 - 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

AU - Salmanton-García, Jon

AU - Marchesi, Francesco

AU - Koehler, Philipp

AU - Weinbergerová, Barbora

AU - Čolović, Natasa

AU - Falces-Romero, Iker

AU - Buquicchio, Caterina

AU - Farina, Francesca

AU - van Praet, Jens

AU - Biernat, Monika M.

AU - Itri, Federico

AU - Prezioso, Lucia

AU - Tascini, Carlo

AU - Vena, Antonio

AU - Romano, Alessandra

AU - Delia, Mario

AU - Dávila-Valls, Julio

AU - Martín-Pérez, Sonia

AU - Lavilla-Rubira, Esperanza

AU - Adžić-vukičević, Tatjana

AU - García-Bordallo, Daniel

AU - López-García, Alberto

AU - Criscuolo, Mariana

AU - Petzer, Verena

AU - Fracchiolla, Nicola S.

AU - Espigado, Ildefonso

AU - Sili, Uluhan

AU - Meers, Stef

AU - Erben, Nurettin

AU - Cattaneo, Chiara

AU - Tragiannidis, Athanasios

AU - Gavriilaki, Eleni

AU - Schönlein, Martin

AU - Mitrovic, Mirjana

AU - Pantic, Nikola

AU - Merelli, Maria

AU - Labrador, Jorge

AU - Hernández-Rivas, José Ángel

AU - Glenthøj, Andreas

AU - Fouquet, Guillemette

AU - del Principe, Maria Ilaria

AU - Dargenio, Michelina

AU - Calbacho, María

AU - Besson, Caroline

AU - Kohn, Milena

AU - Gräfe, Stefanie

AU - Hersby, Ditte Stampe

AU - Arellano, Elena

AU - Çolak, Gökçe Melis

AU - Wolf, Dominik

AU - Marchetti, Monia

AU - Nordlander, Anna

AU - Blennow, Ola

AU - Cordoba, Raul

AU - Mišković, Bojana

AU - Mladenović, Miloš

AU - Bavastro, Martina

AU - Limongelli, Alessandro

AU - Rahimli, Laman

AU - Pagano, Livio

AU - Cornely, Oliver A.

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Methods: Clinical data from patients treated 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 severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. Results: 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 (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. Conclusions: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

AB - Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Methods: Clinical data from patients treated 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 severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. Results: 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 (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. Conclusions: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

KW - Antiviral

KW - COVID-19

KW - Haematology

KW - Malignancy

KW - Molnupiravir

KW - Nirmatrelvir

KW - Ritonavir

KW - SARS-CoV-2

U2 - 10.1016/j.ijantimicag.2023.106952

DO - 10.1016/j.ijantimicag.2023.106952

M3 - Journal article

C2 - 37582478

AN - SCOPUS:85170083215

VL - 62

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

SN - 0924-8579

IS - 4

M1 - 106952

ER -