UCLA study finds no significant benefit of paxlovid for vaccinated older adults

Paxlovid does not significantly reduce COVID-19 hospitalization and mortality among vaccinated older adults, according to new UCLA-led research.

The study questions the assumption that Paxlovid's effectiveness in reducing COVID-19 hospitalizations and deaths in unvaccinated adults also applies to vaccinated adults. Pfizer's 2022 clinical trial found reduced COVID-19 hospitalization in unvaccinated middle-aged adults; while a subsequent 2024 clinical trial found no significant reduction in vaccinated middle-aged adults. Since most older Americans have already received two or more COVID-19 vaccines, Paxlovid's effectiveness on vaccinated older adults has remained an important unanswered question.

"Our study effectively rules out the notion that Paxlovid causes large reductions in COVID-19 hospitalization in vaccinated older adults," Mafi said. "While we cannot rule out a small reduction in COVID-19 hospitalization, our results indicate that at best, Paxlovid's potential effect on COVID-19 hospitalization among vaccinated older adults is four times weaker than the effect originally reported in Pfizer's 2022 clinical trial."

The findings, to be published in the peer-reviewed JAMA, "are important because Pfizer's 2022 clinical trial continues to serve as the foundation of evidence supporting Paxlovid's perceived effectiveness, list price of about $1,650 per treatment course, and widespread global use," Mafi said.

To determine the association between Paxlovid and COVID-19-related hospitalizations, all-cause hospitalizations and all-cause mortality outcomes, the researchers exploited a natural experiment in Ontario, Canada. Between April 1 and November 30, 2022, Ontario implemented an age-restrictive policy on access to Paxlovid-reserving it for symptomatic, COVID-19-positive adults aged 70 years and older, unless they were immunocompromised or had other risk factors. The researchers used data from several Ontario health databases linked by ICES, the major steward of Ontario health data.

By restricting Paxlovid access by age, the policy created a rare natural experiment that the study analyzed to evaluate Paxlovid's impact on key health outcomes, effectively avoiding the common observational research pitfall known as unobserved confounding. "Unobserved confounding is a problem because the decision to use Paxlovid is not random, and the factors that influence its use are able to influence the risk of hospitalization or mortality," said study co-author Sitaram Vangala, biostatistician in the Department of Medicine Statistics Core.

The study is limited by a lack of individual patient-level data regarding symptoms, timing of previous COVID-19 vaccinations, receipt of Paxlovid, and medication adherence.

Additional co-authors Manying Cui and Artem Romanov of UCLA, and Dr. Moira Kapral and Dr. Peter Wu of the University of Toronto. Dr. Wu is affiliated with ICES.

The study was funded by the Commonwealth Fund and a National Institute on Aging Beeson Emerging Leaders in Aging Research Career Development Award (K76AG064392-01A1). This study was also supported by ICES, which is supported by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC).

Source:

University of California - Los Angeles Health Sciences

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