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.
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Salmanton-García J, Marchesi F, Koehler P, Weinbergerová B, Čolović N, Falces-Romero I, Buquicchio C, Farina F, van Praet J, Biernat MM, Itri F, Prezioso L, Tascini C, Vena A, Romano A, Delia M, Dávila-Valls J, Martín-Pérez S, Lavilla-Rubira E, Adžić-Vukičević T, García-Bordallo D, López-García A, Criscuolo M, Petzer V, Fracchiolla NS, Espigado I, Sili U, Meers S, Erben N, Cattaneo C, Tragiannidis A, Gavriilaki E, Schönlein M, Mitrovic M, Pantic N, Merelli M, Labrador J, Hernández-Rivas J, Glenthøj A, Fouquet G, Del Principe MI, Dargenio M, Calbacho M, Besson C, Kohn M, Gräfe S, Hersby DS, Arellano E, Çolak GM, Wolf D, Marchetti M, Nordlander A, Blennow O, Cordoba R, Mišković B, Mladenović M, Bavastro M, Limongelli A, Rahimli L, Pagano L, Cornely OA
Int J Antimicrob Agents 62 (4) 106952 [2023-10-00; online 2023-08-13]
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. 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. 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. 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.
Topics: Register-based research
PubMed 37582478
DOI 10.1016/j.ijantimicag.2023.106952
Crossref 10.1016/j.ijantimicag.2023.106952
pii: S0924-8579(23)00231-5