Increased Nirmatrelvir-Ritonavir Prescriptions Did Not Reduce COVID-19 Hospitalization, Mortality
Researchers compared hospitalization and mortality outcomes of older adults with and without restricted access to nirmatrelvir-ritonavir.
Increased rates of nirmatrelvir-ritonavir prescriptions did not lead to reduced COVID-19–related hospitalization or mortality among older adult patients, according to data published in JAMA.1 Despite double the rate of prescriptions among those aged 70 to 74, outcomes were insignificant when compared with patients aged 65 to 69.
“Randomized clinical trials of nirmatrelvir-ritonavir found reduced COVID-19–related hospitalizations among unvaccinated patients but not vaccinated patients,” wrote authors of the study. “Although advanced age is the strongest predictor of severe COVID-19, the median ages of the trial participants were 42 and 46 years. It remains unknown whether the results of these trials generalize to older and highly vaccinated populations.”
Nirmatrelvir-ritonavir (Paxlovid) is an oral combination drug approved to treat COVID-19 in December 2021. It is currently used to treat patients over 12 who test positive for SARS-CoV-2 and are not hospitalized for it.2 Nirmatrelvir-ritonavir was given emergency use authorization upon its initial approval and it remains the leading antiviral treatment option for preventing severe COVID-19–related illness.3
This natural experiment consisted of Ontario-based patients 65 to 74 years old and was conducted from April 1, 2022, to November 30, 2022. | image credit: bizoo_n / stock.adobe.com
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Just a few months before the approval of nirmatrelvir-ritonavir, the FDA approved the first vaccine to keep patients protected against COVID-19.4 Since treatment and protection for the disease has been readily available, researchers have discovered varied outcomes among both vaccinated and unvaccinated patients using nirmatrelvir-ritonavir.
Their goal was to expand upon evidence regarding hospitalization and mortality in patients who have had COVID-19. To do so, they aimed to find an association between nirmatrelvir-ritonavir and COVID-19–related hospitalizations (primary outcome), all-cause hospitalizations, and all-cause mortality.
“We made use of a natural experiment to compare hospitalization and mortality outcomes in vaccinated older adults with vs without restricted access to nirmatrelvir-ritonavir,” they wrote.1 This natural experiment consisted of Ontario-based patients 65 to 74 years old and was conducted from April 1, 2022, to November 30, 2022.
“During this time, Ontario implemented an age-restrictive policy, with nirmatrelvir-ritonavir being reserved for symptomatic adults aged 70 years or older with positive COVID-19 test results, unless they were immunocompromised or had less than 3 COVID-19 vaccinations plus another risk factor,” added the study authors. They compared patient outcomes of participants “just below” and “just above” 70 years old who had similar characteristics, aside from rate of nirmatrelvir-ritonavir prescription. Participants were separated into 2 age groups: 65-69 and 70-74.
The study population included 1,620,884 patients 65 to 74 years old (52.2% women, 87.5% with at least 2 COVID-19 vaccines). “Nirmatrelvir-ritonavir prescriptions (n = 19,868) increased with age, rising more among patients just above vs just below age 70 years,” wrote the authors.1
“Although hospitalization and mortality outcomes also rose with age, there were no significant differences just below vs just above age 70 years in COVID-19–related hospitalizations, all-cause hospitalizations, or all-cause mortality,” they contined.
Researchers noted that these outcomes were similarly insignificant in 2021, before the availability of nirmatrelvir-ritonavir and other approved COVID-19 treatments. At a more than doubled rate of nirmatrelvir-ritonavir prescriptions, the group of patients over 70 saw no significant reductions in COVID-19–related hospitalizations, all-cause mortality, and hospitalizations in general when compared with patients under 70.
Prior to the study, researchers noted unlikely outcomes of nirmatrelvir-ritonavir treatment for unvaccinated and vaccinated patients. Now, moving the focus to older populations at greater risk of COVID-19 complications, they found further evidence that skews their understanding of nirmatrelvir-ritonavir’s effects. With these insignificant findings amongst an at-risk group, they believe future research should focus on older adult patients over the age of 65.
“A more than doubled rate of nirmatrelvir-ritonavir prescriptions was not associated with reductions in hospitalizations or mortality among highly vaccinated older adults in Ontario,” concluded the authors.1 “Further randomized clinical trials investigating nirmatrelvir-ritonavir’s effects in high-risk subgroups are needed.”
READ MORE: COVID-19 Resource Center
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