Study questions Paxlovid’s COVID-19 ‘usefulness’

A new study has suggested nirmatrelvir-ritonavir alleviates COVID-19 symptoms just one day earlier than a placebo drug, as international scientists continue to examine its effectiveness.
 
However, the authors say vulnerable patients are still most likely to get the greatest benefit from the antiviral, sold as Paxlovid, including the elderly or immunocompromised.
 
More than 450,000 prescriptions have been issued since the medication was added to the PBS in May 2022, but infectious diseases physician Associate Professor Paul Griffin said it is ‘increasingly apparent’ GPs should only use the antivirals for those who are at the greatest risk.
 
‘In people outside of those very significant risk factors, it seems that we don’t really see any evidence of a benefit, and so that’s why they have been prioritised as high-risk groups,’ he told newsGP.
 
‘It’s not because we’re trying to withhold something that could help them, but because it just doesn’t seem to make much of a difference in the absence of significant risk factors.
 
‘In the absence of those risk factors, they’re just not likely to work, but I think in the right patients, there’s still clearly a benefit and we need to make sure we use them.’
 
Published in the New England Journal of Medicine this month, the study split almost 1300 patients into two groups, each receiving either nirmatrelvir-ritonavir or a placebo every 12 hours for five days.
 
All patients had confirmed COVID-19 with symptom onset within the past five days, with the study carried out between July 2021–22.
 
It included those who were fully vaccinated and had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated or had not been vaccinated within the previous year.
 
The median age of participants was 42 years, and just 5% were 65 years or older.
 
Over 28 days, the median time it took for symptoms to alleviate was 12 days in the Paxlovid group and 13 days in the placebo group.
 
Five participants in the nirmatrelvir-ritonavir group and 10 in the placebo group were hospitalised for COVID or died from any cause by the end of the study.
 
However, ‘as with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir-ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit,’ the authors said.
 
Associate Professor Griffin said it is vital GPs continue to offer antivirals to those at-risk patients in a timely manner.
 
‘In this study, it was taken within five days of symptom onset and that’s probably a bit long, because really, we should be trying to initiate them as early as possible,’ he said.
 
‘It’s likely that the time from infection to initiation is probably one of the biggest determinants of how well they’re likely to work.
 
‘We should really be trying to make sure that those patients who are likely to be eligible, those who do have very high risk, are educated on how to find out if they have COVID and how to get those antivirals.’
 
The study’s release comes after eligibility for antiviral prescriptions for COVID-19 was altered last month, now requiring molnupiravir (sold as Lagevrio) to be used only when Paxlovid is contraindicated.
 
The details and reasons of contraindications to Paxlovid must also be documented in the patient’s medical records.
 
PBS eligibility criteria for nirmatrelvir-ritonavir continue to include adults 70 years or older with mild-to-moderate COVID-19, as well as those 50 years or older with two additional risk factors.
 
Professor Mark Morgan, Chair of RACGP Expert Committee – Quality Care, told newsGP it remains unclear why these trial results were not published earlier.
 
‘The numbers of participants and between group differences were too small to be clear if this difference occurred by chance or because of the treatment,’ he said.
 
‘Similarly, there was no difference in the rates of viral load rebound or symptoms rebound after completion of the course of Paxlovid.’
 
The nirmatrelvir-ritonavir researchers said in the future, more trials are needed to evaluate different treatment durations and combination therapies compared with monotherapies, in a bid to understand how best to treat patients.
 
‘Finally, we should require longer-term follow-up of participants in trials to determine whether the treatment of acute infection prevents post-COVID-19 conditions,’ they said.
 
‘Although we have learned an amazing amount about SARS-CoV-2 therapy, the final chapters on treating COVID-19 are yet to be written.’
 
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