Paxlovid associated with decreased hospitalization rate among adults with COVID-19 — United States, April–September 2022

Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system

“…8 However, such patterns are inconsistent across reports. One US study estimated greater effectiveness among adults aged <65 years than those aged 65–79 or ≥80 years, while another US study 14 and a separate study in Hong Kong 12 did not identify differences in effectiveness across subgroups defined by age, immunity, or presence of comorbidities. In further contrast to findings in Israel, studies in Hong Kong 11,12 which have enrolled the most elderly samples (majority of treated cases aged >70 years) with the lowest vaccine coverage (33–42% considered fully vaccinated against COVID-19) have generated the lowest estimates of effectiveness of nirmatrelvir-ritonavir, spanning 21–33%.…”

“…Because the perceived risk for a cases to progress to severe disease likely factors into clinical decision-making around nirmatrelvir-ritonavir prescribing and cases’ adherence to treatment, controlling for potential differences in clinical status among cases who receive or do not receive treatment is important for causal inference in pharmacoepidemiologic studies. Whereas we identify time from symptom onset as a potential modifier of treatment effectiveness, symptoms data were lacking in prior observational studies from all 8–12,14 or most 13 cases analyzed. Our estimate of 53.6% effectiveness against the primary endpoint for cases treated at any time in their clinical course aligns with estimates of 45–51% effectiveness against hospitalization in other US observational studies which did not collect symptoms data or restrict according to symptom onset timing.…”

“…Matching cases within regression strata provided an opportunity to account for potential interactions among variables associated with cases’ likelihood of receiving treatment, as observed within our sample, as well as potential interactions among these variables influencing cases’ risk for adverse clinical outcomes. 35,36 Covariate adjustment 8,10,14 and inverse probability weighting 9,11 frameworks applied in other studies may have afforded less flexibility as a strategy to mitigate confounding.…”

“…In recent observational studies, nirmatrelvir-ritonavir was estimated to confer 21-79% reductions in risk of hospital admission or other severe endpoints, with the strongest evidence of clinical benefit among high-risk subgroups including older adult cases, obese cases, and cases not known to have immunity to SARS-CoV-2 from prior infection or vaccination. [8][9][10][11][12][13][14] Factors explaining this wide range of effectiveness estimates remain uncertain. Whereas timing of administration may be of crucial importance to the effectiveness of antiviral therapies, prior effectiveness studies have lacked symptoms data, making it difficult to compare results across studies potentially enrolling cases with heterogeneous clinical status.…”

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

“…In a similar retrospective work, Shah et al analyzed the data of a population of 699,848 Americans who were diagnosed with COVID-19 in the spring and summer of 2022, and evaluated the proportion of them who received nirmatrelvir/ritonavir, and also how nirmatrelvir/ritonavir altered the course of disease [57] . They observed that nirmatrelvir/ritonavir, in general as well as with various demographic adjustments, was of the ability to significantly reduce the rate of admission to hospital, which could be interpreted into its ability to inhibit the progression toward severe COVID-19; regarding their findings, they insisted on a more pervasive use of this medication in outpatient settings [57] .…”