Study: No large benefit from Paxlovid among COVID-vaccinated older adults
Key takeaways:
- Paxlovid may not decrease the risk for hospitalization or death among older adults who are vaccinated.
- Unvaccinated older adults are more likely to see a benefit, the study found.
Paxlovid may not decrease the risk for hospitalization or death in older adults vaccinated against COVID-19 as much as previously thought, according to research published in JAMA.
“Since the strongest predictor of severe COVID-19 is advanced age, it has been crucial to obtain evidence on whether the results of the Pfizer trials” — which showed Paxlovid reduced COVID-19 hospitalizations and deaths in unvaccinated adults — “generalized to older and vaccinated populations,” John Mafi, MD, MPH, associate professor-in-residence of medicine at the David Geffen School of Medicine at UCLA, said in a press release.
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The FDA initially granted an emergency use authorization for Paxlovid in 2021 for use in high-risk people aged 12 years or older, which was later expanded for qualified patients immediately after testing positive for SARS-CoV-2. The treatment, a combination of the drugs nirmatrelvir and ritonavir, was fully approved by the FDA in May 2023.
Early evidence showed that Paxlovid reduced the risk for severe disease, hospitalization and death. Some recent studies, however, including results from Pfizer studies conducted in 2022 and 2023, have called into question the efficacy of the medication for older adults and, particularly, vaccinated older adults, which Mafi and colleagues noted in the new study.
Mafi and colleagues analyzed aggregate summary-level data from Ontario health care databases on nearly 20,000 people aged 65 years to 74 years who were prescribed Paxlovid after a positive COVID-19 test between April 1, 2022, and Nov. 30, 2022. According to the study, Ontario restricted age access to Paxlovid during this time period, reserving the drug for symptomatic, COVID-19-positive adults aged 70 years or older, unless they had other risk factors or had received less than three COVID-19 vaccines. Most of the older adults had received at least two COVID-19 vaccines, the researchers noted.
To determine whether the drug had an effect on COVID-related hospitalization, all-cause hospitalization and all-cause mortality, the researchers used a “fuzzy regression discontinuity design” to compare the outcomes of people older or younger than age 70 years who were similar aside for whether they had received Paxlovid.
The researchers reported that patients aged older than 70 years received 121.9 more prescriptions per 100,000 patients per month (95% CI, 95.7 to 148.1). Hospitalization and mortality increased with patient age, but there were no significant differences between the older and younger groups in the three outcomes: The younger group saw 3.4 fewer COVID-19 hospitalizations per 100,000 patients per month compared with the older group (95% CI, –1.3 to 8.1); 8.9 fewer all-cause hospitalizations (95% CI, –35 to 52.7); and 6.1 fewer all-cause mortalities (95% CI, –2.7 to 14.9).
The researchers concluded that although there were more than double the prescriptions of Paxlovid among older adults in the study, the drug did not have a significant effect among the age group.
At best, Mafi and colleagues wrote, Paxlovid could reduce COVID-19-related hospitalization by 1.3 percentage points, or 4 times less than the 5.5 percentage-point risk reduction reported in Pfizer’s original trial among unvaccinated adults.
“Our study effectively rules out the notion that Paxlovid causes large reductions in 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.”
References:
- Hammon J, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2118542.
- Hammond J, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2309003.
- Mafi JN, et al. JAMA. 2025;doi:10.1001/jama.2024.28099.
- Paxlovid’s impact on hospitalization and death in COVID-vaccinated older adults far weaker than previously thought. https://www.uclahealth.org/news/release/paxlovids-impact-hospitalization-and-death-covid-vaccinated. Published Feb. 20, 2025. Accessed Feb. 21, 2025.