UCLA examine finds no vital advantage of paxlovid for vaccinated older adults

Paxlovid doesn’t considerably scale back COVID-19 hospitalization and mortality amongst vaccinated older adults, in line with new UCLA-led analysis.

The examine questions the idea that Paxlovid’s effectiveness in decreasing COVID-19 hospitalizations and deaths in unvaccinated adults additionally applies to vaccinated adults. Pfizer’s 2022 medical trial discovered decreased COVID-19 hospitalization in unvaccinated middle-aged adults; whereas a subsequent 2024 medical trial discovered no vital discount in vaccinated middle-aged adults. Since most older Individuals have already acquired two or extra COVID-19 vaccines, Paxlovid’s effectiveness on vaccinated older adults has remained an vital unanswered query.

“Because the strongest predictor of extreme COVID-19 is superior age, it has been essential to acquire proof on whether or not the outcomes of the Pfizer trials generalized to older and vaccinated populations,” mentioned Dr. John Mafi, an affiliate professor-in-residence of drugs within the division of normal inner drugs and well being providers analysis on the David Geffen Faculty of Medication at UCLA and the examine’s lead writer. 

“Our examine successfully guidelines out the notion that Paxlovid causes giant reductions in COVID-19 hospitalization in vaccinated older adults,” Mafi mentioned. “Whereas we can not rule out a small discount in COVID-19 hospitalization, our outcomes point out that at greatest, Paxlovid’s potential impact on COVID-19 hospitalization amongst vaccinated older adults is 4 instances weaker than the impact initially reported in Pfizer’s 2022 medical trial.”

The findings, to be printed within the peer-reviewed JAMA, “are vital as a result of Pfizer’s 2022 medical trial continues to function the muse of proof supporting Paxlovid’s perceived effectiveness, listing worth of about $1,650 per remedy course, and widespread international use,” Mafi mentioned.

Because the examine discovered no vital impact on COVID-19 hospitalizations and deaths amongst vaccinated older adults, our findings underscore the pressing want for additional randomized-clinical trials investigating Paxlovid’s results in higher-risk populations, equivalent to older subgroups who’re frail or immunosuppressed.” 

Dr. Katherine Kahn, distinguished professor of drugs within the normal inner drugs division and the examine’s senior writer

To find out the affiliation between Paxlovid and COVID-19-related hospitalizations, all-cause hospitalizations and all-cause mortality outcomes, the researchers exploited a pure experiment in Ontario, Canada. Between April 1 and November 30, 2022, Ontario carried out an age-restrictive coverage on entry to Paxlovid-reserving it for symptomatic, COVID-19-positive adults aged 70 years and older, except they have been immunocompromised or had different danger elements. The researchers used information from a number of Ontario well being databases linked by ICES, the key steward of Ontario well being information.

They in contrast outcomes of sufferers who have been just under vs simply above 70-years-old who have been plausibly comparable besides for his or her publicity to Paxlovid. The researchers discovered that amongst 1.6 million extremely vaccinated older Ontarians, the coverage to limit Paxlovid to these aged 70, elevated the speed of Paxlovid prescriptions by 118% at age 70. This doubling within the prescription price didn’t, nevertheless, translate into improved COVID-19-related hospitalization, all-cause hospitalization, or all-cause mortality outcomes.

By limiting Paxlovid entry by age, the coverage created a uncommon pure experiment that the examine analyzed to guage Paxlovid’s impression on key well being outcomes, successfully avoiding the widespread observational analysis pitfall generally known as unobserved confounding. “Unobserved confounding is an issue as a result of the choice to make use of Paxlovid shouldn’t be random, and the elements that affect its use are capable of affect the chance of hospitalization or mortality,” mentioned examine co-author Sitaram Vangala, biostatistician within the Division of Medication Statistics Core.

“As a result of entry to Paxlovid on this examine was in impact randomized for these near the age 70 cutoff, our outcomes are unlikely to replicate unobserved confounding,” Vangala mentioned. “This will likely clarify why our outcomes align with the current adverse 2024 medical trial amongst vaccinated middle-aged adults, however not with observational research exhibiting that Paxlovid is related to giant reductions in hospitalization and mortality in vaccinated older adults.”

The examine is restricted by an absence of particular person patient-level information relating to signs, timing of earlier COVID-19 vaccinations, receipt of Paxlovid, and medicine adherence.

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

The examine was funded by the Commonwealth Fund and a Nationwide Institute on Ageing Beeson Rising Leaders in Ageing Analysis Profession Improvement Award (K76AG064392-01A1). This examine was additionally supported by ICES, which is supported by an annual grant from the Ontario Ministry of Well being (MOH) and the Ministry of Lengthy-Time period Care (MLTC).