Paxlovid Tied to Benefits in High-Risk Patients With COVID

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Nirmatrelvir–ritonavir (Paxlovid) is associated with a reduced risk for death or hospitalization in the most extremely vulnerable patients with COVID-19, new research suggests.

In a cohort study from British Columbia, Canada, that included nearly 7000 patients with COVID-19, nirmatrelvir–ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.

“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia in Vancouver, told Medscape Medical News. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”

The study was published online October 2 in JAMA Network Open.

Who Benefits?

The investigators analyzed medical records for 6866 patients in British Columbia (median age, 70 years; 57% women) who presented between February 1, 2022, and February 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.

Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.

The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Treatment with nirmatrelvir–ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference [RD], −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.

The results were “robust across sex and older vs younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”

The combination of nirmatrelvir–ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dormuth.

British Columbia’s eligibility criteria for nirmatrelvir–ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.

Before the study, a common view was that patients age 70 and older would benefit from the drug, said Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”

The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir–ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”

“Signal Toward Benefit”

Commenting on the findings for Medscape, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic in Ohio, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.”

“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these post-market studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”

Duggal was a co-investigator on a recent study of more than 68,000 patients that showed that nirmatrelvir–ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.

“In all groups, there was a signal toward benefit,” said Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”

The study was supported by funding from the British Columbia Ministry of Health. Dormuth and Duggal report no relevant financial relationships.

JAMA Netw Open. Published October 2, 2023. Full text

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