A groundbreaking UCLA-led study has revealed that Paxlovid, the widely prescribed COVID-19 antiviral medication, shows substantially weaker effectiveness in reducing hospitalizations and deaths among vaccinated older adults than previously believed.
The research, set to be published in JAMA, challenges the widespread assumption about Paxlovid's universal effectiveness, particularly in populations different from those in Pfizer's original clinical trials. The findings carry significant implications for clinical practice and healthcare spending, given Paxlovid's current list price of approximately $1,650 per treatment course.
Key Research Findings
The study analyzed data from 1.6 million highly vaccinated older adults in Ontario, Canada, taking advantage of a natural experiment created by the province's age-restrictive policy. Between April and November 2022, Ontario limited Paxlovid access to COVID-19-positive adults aged 70 and older, except for those with specific risk factors.
This policy created a unique opportunity to compare outcomes between patients just below and above the age threshold. While the restriction led to a 118% increase in Paxlovid prescriptions for those aged 70 and above, researchers found no significant improvement in COVID-19-related hospitalizations, all-cause hospitalizations, or mortality rates.
Methodological Strength and Clinical Implications
Dr. John Mafi, associate professor at the David Geffen School of Medicine at UCLA and the study's lead author, emphasized the significance of their findings: "Our study effectively rules out the notion that Paxlovid causes large reductions in COVID-19 hospitalization in vaccinated older adults. At best, Paxlovid's potential effect is four times weaker than the effect originally reported in Pfizer's 2022 clinical trial."
The research methodology notably addressed a common limitation in observational studies known as unobserved confounding. As study co-author Sitaram Vangala explained, the age-based restriction created an essentially randomized environment for those near the age 70 cutoff, strengthening the reliability of the results.
Future Research Directions
Dr. Katherine Kahn, distinguished professor of medicine and the study's senior author, highlighted the need for further investigation: "Our findings underscore the urgent need for additional randomized clinical trials investigating Paxlovid's effects in higher-risk populations, such as older subgroups who are frail or immunosuppressed."
The study's results align with a recent 2024 clinical trial that found no significant reduction in COVID-19 hospitalization among vaccinated middle-aged adults, suggesting a consistent pattern across different vaccinated populations.
Study Limitations
While comprehensive, the research had some limitations, including the absence of individual patient-level data regarding symptoms, timing of previous COVID-19 vaccinations, actual receipt of Paxlovid, and medication adherence. These factors warrant consideration in future studies to further refine our understanding of Paxlovid's role in COVID-19 treatment.
