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

J 2023

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

SALMANTON-GARCÍA, Jon, Francesco MARCHESI, Philipp KOEHLER, Barbora WEINBERGEROVÁ, Natasa ČOLOVIĆ et. al.

Basic information

Original name

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

Authors

SALMANTON-GARCÍA, Jon, Francesco MARCHESI, Philipp KOEHLER, Barbora WEINBERGEROVÁ (203 Czech Republic, belonging to the institution), 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, Hernández-Rivas JOSÉ-ÁNGEL, Andreas GLENTHØJ, Guillemette FOUQUET, Maria Ilaria del PRINCIPE, Michelina DARGENIO, María CALBACHO, Caroline BESSON, Milena KOHN, Stefanie GRÄFE, Ditte Stampe HERSBY, Elena ARELLANO, Gökçe Melis ÇOLAK, Dominik WOLF, Monia MARCHETTI, Anna NORDLANDER, Ola BLENNOW, Raul CORDOBA, Bojana MIŠKOVIĆ, Miloš MLADENOVIĆ, Martina BAVASTRO, Alessandro LIMONGELLI, Laman RAHIMLI, Livio PAGANO and Oliver A CORNELY

Edition

International Journal of Antimicrobial Agents, AMSTERDAM, ELSEVIER, 2023, 0924-8579

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.800 in 2022

RIV identification code

RIV/00216224:14110/23:00133598

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.ijantimicag.2023.106952

UT WoS

001259236700001

Keywords in English

Molnupiravir; Nirmatrelvir; Ritonavir; SARS-CoV-2; COVID-19; Haematology; Malignancy; Antiviral

Abstract

V originále

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.

Citovat

SALMANTON-GARCÍA, Jon, 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, Hernández-Rivas JOSÉ-ÁNGEL, Andreas GLENTHØJ, Guillemette FOUQUET, Maria Ilaria del PRINCIPE, Michelina DARGENIO, María CALBACHO, Caroline BESSON, Milena KOHN, Stefanie GRÄFE, Ditte Stampe HERSBY, Elena ARELLANO, Gökçe Melis ÇOLAK, Dominik WOLF, Monia MARCHETTI, Anna NORDLANDER, Ola BLENNOW, Raul CORDOBA, Bojana MIŠKOVIĆ, Miloš MLADENOVIĆ, Martina BAVASTRO, Alessandro LIMONGELLI, Laman RAHIMLI, Livio PAGANO and Oliver A CORNELY. 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. International Journal of Antimicrobial Agents. AMSTERDAM: ELSEVIER, 2023, vol. 62, No 4, p. 1-9. ISSN 0924-8579. Available from: https://dx.doi.org/10.1016/j.ijantimicag.2023.106952.

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   author = {SalmantonandGarcía, Jon and Marchesi, Francesco and Koehler, Philipp and Weinbergerová, Barbora and Čolović, Natasa and FalcesandRomero, Iker and Buquicchio, Caterina and Farina, Francesca and Praet, Jens van and Biernat, Monika M and Itri, Federico and Prezioso, Lucia and Tascini, Carlo and Vena, Antonio and Romano, Alessandra and Delia, Mario and DávilaandValls, Julio and MartínandPérez, Sonia and LavillaandRubira, Esperanza and Adžićandvukičević, Tatjana and GarcíaandBordallo, Daniel and LópezandGarcía, Alberto and Criscuolo, Mariana and Petzer, Verena and Fracchiolla, Nicola S and Espigado, Ildefonso and Sili, Uluhan and Meers, Stef and Erben, Nurettin and Cattaneo, Chiara and Tragiannidis, Athanasios and Gavriilaki, Eleni and Schönlein, Martin and Mitrovic, Mirjana and Pantic, Nikola and Merelli, Maria and Labrador, Jorge and JoséandÁngel, HernándezandRivas and Glenthøj, Andreas and Fouquet, Guillemette and Principe, Maria Ilaria del and Dargenio, Michelina and Calbacho, María and Besson, Caroline and Kohn, Milena and Gräfe, Stefanie and Hersby, Ditte Stampe and Arellano, Elena and Çolak, Gökçe Melis and Wolf, Dominik and Marchetti, Monia and Nordlander, Anna and Blennow, Ola and Cordoba, Raul and Mišković, Bojana and Mladenović, Miloš and Bavastro, Martina and Limongelli, Alessandro and Rahimli, Laman and Pagano, Livio and Cornely, Oliver A},
   article_location = {AMSTERDAM},
   article_number = {4},
   doi = {http://dx.doi.org/10.1016/j.ijantimicag.2023.106952},
   keywords = {Molnupiravir; Nirmatrelvir; Ritonavir; SARS-CoV-2; COVID-19; Haematology; Malignancy; Antiviral},
   language = {eng},
   issn = {0924-8579},
   journal = {International Journal of Antimicrobial Agents},
   title = {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},
   url = {https://www.sciencedirect.com/science/article/pii/S0924857923002315?via%3Dihub},
   volume = {62},
   year = {2023}
}

TY  - JOUR
ID  - 2376658
AU  - Salmanton-García, Jon - Marchesi, Francesco - Koehler, Philipp - Weinbergerová, Barbora - Čolović, Natasa - Falces-Romero, Iker - Buquicchio, Caterina - Farina, Francesca - Praet, Jens van - Biernat, Monika M - Itri, Federico - Prezioso, Lucia - Tascini, Carlo - Vena, Antonio - Romano, Alessandra - Delia, Mario - Dávila-Valls, Julio - Martín-Pérez, Sonia - Lavilla-Rubira, Esperanza - Adžić-vukičević, Tatjana - García-Bordallo, Daniel - López-García, Alberto - Criscuolo, Mariana - Petzer, Verena - Fracchiolla, Nicola S - Espigado, Ildefonso - Sili, Uluhan - Meers, Stef - Erben, Nurettin - Cattaneo, Chiara - Tragiannidis, Athanasios - Gavriilaki, Eleni - Schönlein, Martin - Mitrovic, Mirjana - Pantic, Nikola - Merelli, Maria - Labrador, Jorge - José-Ángel, Hernández-Rivas - Glenthøj, Andreas - Fouquet, Guillemette - Principe, Maria Ilaria del - Dargenio, Michelina - Calbacho, María - Besson, Caroline - Kohn, Milena - Gräfe, Stefanie - Hersby, Ditte Stampe - Arellano, Elena - Çolak, Gökçe Melis - Wolf, Dominik - Marchetti, Monia - Nordlander, Anna - Blennow, Ola - Cordoba, Raul - Mišković, Bojana - Mladenović, Miloš - Bavastro, Martina - Limongelli, Alessandro - Rahimli, Laman - Pagano, Livio - Cornely, Oliver A
PY  - 2023
TI  - 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
JF  - International Journal of Antimicrobial Agents
VL  - 62
IS  - 4
SP  - 1-9
EP  - 1-9
PB  - ELSEVIER
SN  - 09248579
KW  - Molnupiravir
KW  - Nirmatrelvir
KW  - Ritonavir
KW  - SARS-CoV-2
KW  - COVID-19
KW  - Haematology
KW  - Malignancy
KW  - Antiviral
UR  - https://www.sciencedirect.com/science/article/pii/S0924857923002315?via%3Dihub
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.
ER  -

SALMANTON-GARCÍA, Jon, Francesco MARCHESI, Philipp KOEHLER, Barbora WEINBERGEROVÁ, Natasa ČOLOVI$\backslash$'C, 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 ADŽI$\backslash$'C-VUKIČEVI$\backslash$'C, 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, Hernández-Rivas JOSÉ-ÁNGEL, Andreas GLENTHØJ, Guillemette FOUQUET, Maria Ilaria del PRINCIPE, Michelina DARGENIO, María CALBACHO, Caroline BESSON, Milena KOHN, Stefanie GRÄFE, Ditte Stampe HERSBY, Elena ARELLANO, Gök$\backslash$c ce Melis $\backslash$C COLAK, Dominik WOLF, Monia MARCHETTI, Anna NORDLANDER, Ola BLENNOW, Raul CORDOBA, Bojana MIŠKOVI$\backslash$'C, Miloš MLADENOVI$\backslash$'C, Martina BAVASTRO, Alessandro LIMONGELLI, Laman RAHIMLI, Livio PAGANO and Oliver A CORNELY. 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. \textit{International Journal of Antimicrobial Agents}. AMSTERDAM: ELSEVIER, 2023, vol.~62, No~4, p.~1-9. ISSN~0924-8579. Available from: https://dx.doi.org/10.1016/j.ijantimicag.2023.106952.

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