Today in JAMA Network Open, an observational Canadian study ties the antiviral drug combo nirmatrelvir-ritonavir (Paxlovid) to a lower risk of hospitalization or death only in very high-risk COVID-19 patients with weakened immune systems.
University of British Columbia researchers in Vancouver analyzed rates of severe COVID-19 outcomes among 6,866 adult COVID-19 patients by their vulnerability to severe disease and immune system status from February 1, 2022, to February 3, 2023, a period dominated by the Omicron variant. The team classified the patients into one of four groups given early priority for COVID-19 vaccination.
There were three clinically extremely vulnerable (CEV) patient groups, including those with severely impaired immune systems (CEV1); those with moderately weakened immune systems (CEV2); and those with healthy immune systems but underlying high-risk conditions (CEV3). A fourth category included unvaccinated, non-CEV patients aged 70 years and older with other chronic conditions given wider access to Paxlovid (EXEL).
Recipients of Paxlovid were matched to patients in the same vulnerability group. The median age was 70 years, and 56.6% were women.
Drug benefited only extremely vulnerable patients
Relative to no treatment, Paxlovid therapy was linked to statistically significant reductions in hospitalization and all-cause death by 28 days in the CEV1 group (560 patients; risk difference [RD], -2.5%) and the CEV2 group (2,628; RD, -1.7%).
Stratified analysis of individuals according to vulnerability to complications from COVID-19 is crucial to understanding which individuals should use nirmatrelvir and ritonavir.
Among CEV3 participants, the RD was -1.3%, but the results were not statistically significant (2,100 patients; 95% confidence interval [CI], -2.8% to 0.1%). Paxlovid was associated with a higher risk of hospitalization or death in the EXEL group (RD, 1.0%), but the findings were also not significant (1,578; 95% CI, -0.9% to 2.9%).
"In this study, treatment with nirmatrelvir and ritonavir was not associated with reduced risk of death or hospitalization among individuals who were not extremely vulnerable to complications from COVID-19 infection, regardless of age," the study authors wrote. "Stratified analysis of individuals according to vulnerability to complications from COVID-19 is crucial to understanding which individuals should use nirmatrelvir and ritonavir."
The researchers noted that protective associations with Paxlovid have varied across different study populations and study periods, which they said suggests that the drug's benefit-risk profile depends on susceptibility to COVID-19 complications. "Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials," they wrote.