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The benefit of nirmatrelvir-ritonavir (Paxlovid) for high-risk COVID-19 outpatients appears to extend to younger vaccinated adults with serious comorbidities, retrospective data suggested.

In a propensity-score matched analysis of vaccinated adults ages 50 and under, treatment with the antiviral was associated with a 32% lower risk of an emergency department (ED) visit, hospitalization, or death within 30 days of COVID-19 illness (OR 0.683, 95% CI 0.540-0.864, P=0.001), Jeremy Faust, MD, of Brigham and Women's Hospital in Boston, and colleagues reported.

Among the more than 5,000 matched COVID outpatients, 4.9% of those prescribed nirmatrelvir-ritonavir within 5 days of a positive test met that primary composite outcome versus 7.0% of those who did not receive a prescription for the drug, they detailed in .

However, where there was adequate power for subgroup analysis, the benefit with nirmatrelvir-ritonavir was only seen among COVID-19 patients with certain comorbidities.

For example, a reduction in risk was seen for individuals with cancer (OR 0.692, 95% CI 0.472-0.987), cardiovascular disease (OR 0.629, 95% CI 0.461-0.858), or both (OR 0.432, 95% CI 0.275-0.677), but not for those with chronic lower respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD), a group that comprised over 30% of the matched study population.

Number needed to treat (NNT) analyses showed a reduction in one primary outcome event with nirmatrelvir/ritonavir for every 30 patients with heart disease and for every 45 with documented cancer.

"While our data suggest a role for NMV-r [nirmatrelvir/ritonavir] in some younger vaccinated individuals, it is important to emphasize that both the pre- and the post-matched cohort had an extremely high rate of serious medical comorbidities compared to the general population," wrote Faust and colleagues, highlighting that a third of the matched cohort had documented cancer. "As a result, the treated patients in this cohort were largely in line with the intent of the emergency use authorization."

In terms of prior healthcare system use, nirmatrelvir-ritonavir's benefit was seen both in patients with (OR 0.584, 95% CI 0.434-0.787) and without (OR 0.466, 95% CI 0.261-0.834) an ED visit or hospitalization in the last 3 years, with the NNT analysis showing one event prevented for every 19 and 79 treated with the antiviral, respectively.

No benefit with nirmatrelvir/ritonavir was observed in patients without serious comorbidities, Faust and colleagues found.

"In the future, the need for stewardship and more careful resource allocation are anticipated to increase, as decreases in government funding for COVID-19 treatments are expected," the study authors wrote. "Clinicians and policymakers should consider these findings, so that vital treatments are prescribed for those who need them (including those who have been underserved) and not wasted on those who stand to gain no benefit."

Moreover, they added, there is the possibility of harm due to nirmatrelvir-ritonavir-associated side effects and the potential for symptom rebound, which needs to be weighed against a possible benefit.

For their study, the researchers used the TriNetX database to examine vaccinated individuals ages 18 to 50 with a positive COVID-19 test from December 2021 to July 2022. This included 2,547 patients who received a prescription for nirmatrelvir/ritonavir within 5 days of their illness and 83,572 patients who did not.

Patients who received a monoclonal antibody, convalescent plasma, or molnupiravir were excluded.

After propensity-score matching, patients had a mean age of about 38 years, two-thirds were women, and about three-fourths were white. Comorbidities included chronic lower respiratory disease in 31%, hypertension in 27%, hyperlipidemia in 25%, and diabetes in 13%.

For components of the primary outcome, patients prescribed nirmatrelvir/ritonavir had significantly fewer all-cause hospitalizations (15 vs 43; P<0.001) and deaths at 30 days (0 vs 10; P=0.002). No significant difference was observed for all-cause ED visits.

Limitations of the study included undetected differences between treated and untreated patients, and possible decreased access for those at highest risk.

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