A 115% increase in nirmatrelvir-ritonavir prescriptions among vaccinated older adults in Ontario may not be associated with significant reductions in hospitalizations or mortality, according to a recent research letter.
In the study, published in JAMA, researchers led by John N. Mafi, of the Division of General Internal Medicine and Health Services Research at the David Geffen School of Medicine at the University of California, Los Angeles, evaluated the association between restricted access to nirmatrelvir-ritonavir and hospitalization and mortality outcomes among older vaccinated adults. While prior randomized clinical trials demonstrated reduced COVID-19–related hospitalizations in unvaccinated patients, the median ages of the patients who participated in those trials were 42 and 46 years, leaving uncertainty about the applicability of these findings to older populations with high vaccination rates.
The researchers utilized a natural experiment based on Ontario’s age-restrictive policy, which limited nirmatrelvir-ritonavir prescriptions to symptomatic adults aged 70 years or older unless they were immunocompromised or had fewer than three COVID-19 vaccinations with an additional risk factor. The researchers analyzed aggregate data from ICES-linked Ontario health databases, focusing on 1.6 million patients aged 65 to 74 years between April 1, 2022, and November 30, 2022.
A fuzzy regression discontinuity design was applied to compare outcomes in patients just below vs just above the age cutoff of 70 years, assuming similarities between groups aside from their access to the antiviral drug. The researchers assessed 25 patient characteristics to ensure comparability, finding no significant discontinuities at age 70. Additionally, null findings in historical data from 2021, prior to the availability of nirmatrelvir-ritonavir, minimized concerns of imbalances.
The analysis revealed a substantial increase in antiviral prescriptions among patients just older than 70 years, from 106 to 227.9 per 100,000 patients per month—a 115% increase (95% confidence interval [CI] = 95.7–148.1, P < .001). However, this increase did not translate into statistically significant reductions in hospitalizations or mortality. The absolute difference in COVID-19–related hospitalizations was 3.4 per 100,000 patients per month (39.5 vs 42.9, 95% CI = −1.3 to 8.1, P = .15). All-cause hospitalizations showed an absolute difference of 8.9 (979.6 vs 988.4, 95% CI = −35.0 to 52.7, P = .69), while all-cause mortality had an absolute difference of 6.1 (109.6 vs 115.7, 95% CI = −2.7 to 14.9, P = .17).
The estimated treatment effect suggested a nonsignificant increase in COVID-19–related hospitalization risk of 2.8 percentage points per nirmatrelvir-ritonavir prescription (95% CI = −1.3 to 6.9, P = .18). The findings indicated that, despite a marked rise in prescriptions following the policy shift, there were no statistically significant reductions in hospitalization or mortality outcomes among highly vaccinated older adults. The researchers concluded that further randomized clinical trials are needed to assess the potential benefits of nirmatrelvir-ritonavir in high-risk subgroups.
Full disclosures can be found in the published research letter.