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According to a systematic review and meta-analysis, patients with non-severe COVID-19 may avoid hospitalization or death by treatment with nirmatrelvir-ritonavir or molnupiravir.
In studies conducted primarily in unvaccinated patients infected with the delta variant, treatment with nirmatrelvir-ritonavir was associated with a reduction in mortality of 11.7 per 1000 compared with standard treatment or placebo.
“While we acknowledge that the data has been validated in patients with another variant, we expect it is likely still relevant for other variants,” study author Tyler Pitre, MD, told Medscape Medical News. “We present the most recent summary of evidence that suggests benefit for some of these drugs. We hope this will be helpful.
“Most surprising was the lack of effectiveness of remdesivir,” he said. “Remdesivir is currently recommended for non-severe illnesses, but our analysis found no mortality benefit, and there was low-certainty evidence for other important endpoints such as hospitalization and reduced risk of invasive mechanical ventilation.”
The study was published online July 25 in CMAJ.
Benefits of “Probably”
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Pitr and colleagues extracted data from randomized trials comparing antiviral therapy with placebo or standard care from the Epistemonikos COVID-19 L OVE (Living Overview of Evidence) database up to April 25, 2022. Forty-one trials involving 18,568 patients with non-severe COVID-1919 were included in the analysis. Participants ranged in age from 36 to 65, and about half of the participants were male.
The researchers suggested a baseline risk of 13.3 deaths per 1,000 people based on the median risk in the placebo group and the standard care group. Molnupiravir and nirmatrelvir-ritonavir reduced the risk of death (10.9 fewer deaths per 1000 and 11.7 fewer deaths per 1000, respectively) with moderate significance compared with placebo or standard therapy.
In contrast, remdesivir did not affect the risk of mortality, nor did sofosbuvir-daclatasvir or emtricitabine-tenofovir (moderate confidence).
The risk of hospitalization was reduced with nirmatrelvir-ritonavir (46.2 fewer hospitalizations per 1000, high confidence) compared with standard treatment or placebo. Molnupiravir probably reduced risk (16.3 fewer hospitalizations per 1000, moderate confidence) and remdesivir probably reduced risk (39.1 fewer hospitalizations, low confidence).
In addition, nirmatrelvir-ritonavir likely reduced the risk of hospitalization compared to molnupiravir (27.8 fewer hospitalizations per 1000, moderate confidence).
The analysis also showed that molnupiravir likely reduced the need for ventilators (13 fewer events per 1000, moderate confidence) compared with placebo or standard therapy, while remdesivir probably reduced the risk of needing ventilators (11.8 fewer events per 1000, moderate confidence). 1000, moderate confidence). low confidence).
The frequency of adverse events was largely the same for nirmatrelvir-ritonavir and molnupiravir.
Subgroup analyzes of the two studies of remdesivir did not show that age or gender affected the risk of mortality. Only one study of molnupiravir provided subgroup data. In this trial, there was no evidence of an effect of disease on hospitalization rates based on severity, age, or gender.
The analysis will be updated as results from large trials come in, Pitre said.
Current influence “Unknown”
“Adaptive platform trials and large observational studies offer the best opportunity to provide timely evidence for the effectiveness of COVID-19 therapies,” write Corinne Hall, MD, Associate Professor of Emergency Medicine at the University of British Columbia Vancouver, and Andrew McRae. , MD, PhD, Assistant Professor of Emergency Medicine at the University of Calgary, Alberta, in an accompanying editorial. “These studies can be completed in Canada, but must be supported by Canadian research sponsors, healthcare institutions, data custodians, healthcare providers and patients.”
Commenting on the report for Medscape, Robert M. Grossberg, MD, Medical Director of the Montefiore Health System ID Center for Positive Living/Clinic and Associate Professor of Infectious Diseases at the Albert Einstein College of Medicine in New York, said: “This analysis adds support to our current understanding situation with COVID-19 antivirals”.
However, he added: “As the authors note, studies … were conducted on unvaccinated participants before the advent of Omicron. We expect vaccinated people to be less likely to develop serious illness or hospitalization. We also know that these results are less likely with Omicron than with earlier options. So we can expect the impact of these drugs to be much less in the current space as most patients will do well without any antiviral treatment.”
However, Grossberg said other endpoints, such as duration of illness or duration of virus shedding, can influence transmission and should be considered. “Ideally, these drugs are best evaluated directly. This may give a clearer idea of which medication is best.
“The overall benefit of any of these drugs for vaccinated patients with the current variant is unknown,” Grossberg concluded.
The study was conducted without external funding. Pieter and Grossberg reported no relevant financial relationship. Hohl has received grants from the COVID-19 Immunity Task Force, the Canadian Institutes for Health Research, Genome BC, the Michael Smith Foundation for Health Research, and the Canadian Association of Emergency Physicians. McRae has received grants from the Canadian Institute for Health Research and Roche Diagnostics Canada, as well as honoraria from Western University and Servier Pharmaceuticals.
CMAJ. Published online July 25, 2022 Full text
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