Zhou: Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study [Paxlovid]

Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study

Zhou et al., medRxiv, doi:10.1101/2022.09.13.22279908 (Preprint)

Zhou et al., Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19.., medRxiv, doi:10.1101/2022.09.13.22279908 (Preprint)

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Pfizer retrospective 2,811 high risk COVID-19 patients treated with paxlovid in the US, and 10,849 matched controls, showing lower risk of mortality and hospitalization with treatment.

Confounding by contraindication. [Hoertel] find that over 50% of patients that died had a contraindication for the use of Paxlovid. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.

1. Hoertel et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140, Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798450.

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risk of death, 73.0% lower, RR 0.27, p < 0.001, treatment 7 of 2,808 (0.2%), control 100 of 10,849 (0.9%), NNT 149, propensity score matching, day 30.

risk of death, 75.2% lower, RR 0.25, p < 0.001, treatment 5 of 2,808 (0.2%), control 78 of 10,849 (0.7%), NNT 185, propensity score matching, day 15.

risk of hospitalization, 84.0% lower, HR 0.16, p < 0.001, treatment 34 of 2,808 (1.2%), control 752 of 10,849 (6.9%), NNT 17, propensity score matching, Cox proportional hazards, day 30.

risk of hospitalization, 89.0% lower, HR 0.11, p < 0.001, treatment 22 of 2,808 (0.8%), control 708 of 10,849 (6.5%), NNT 17, propensity score matching, Cox proportional hazards, day 15.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Zhou et al., 14 Sep 2022, retrospective, USA, preprint, median age 62.0, 9 authors, study period 22 December, 2021 - 8 June, 2022.

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PhD Xiaofeng Zhou, PhD Scott P Kelly, MD Caihua Liang, MS Ling Li, MS Rongjun Shen, BSN Heidi K Leister-Tebbe, PharmD Steven G Terra, PhD Michael Gaffney, PhD Leo Russo

doi:10.1101/2022.09.13.22279908

Objectives: The aim of this analysis was to describe nirmatrelvir/ritonavir real-world effectiveness in preventing hospitalization among high-risk US COVID-19 patients during SARS-CoV-2 Omicron predominance. Design: An ongoing population-based cohort study with retrospective and prospective collection of electronic healthcare data in the United States. Methods: Data for this analysis were collected from the US Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset during December 22, 2021−June 8, 2022. Key eligibility criteria for inclusion in the database analysis were ≥12-years-old; positive SARS-CoV-2 test, COVID-19 diagnosis, or nirmatrelvir/ritonavir prescription; and high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching (PSM). Immortal time bias was addressed. Outcome measures: Hospitalization rates within 30 (primary analysis) or 15 (sensitivity analysis) days from COVID-19 diagnosis overall and within subgroups were evaluated. Results: Before PSM, the nirmatrelvir/ritonavir group (n=2811) was less racially diverse, older, and had higher COVID-19 vaccination rates and a greater number of comorbidities than the nonnirmatrelvir/ritonavir group (n=194,542). Baseline characteristics were well balanced across groups (n=2808 and n=10,849, respectively) after PSM. Incidence of hospitalization (95% CI) within 30 days was 1.21% (0.84%−1.69%) for the nirmatrelvir/ritonavir group and 6.94% (6.03%−7.94%) for the nonnirmatrelvir/ritonavir group, with a hazard ratio (95% CI) of 0.16 (0.11−0.22; 84% relative risk reduction). Incidence within 15 days was 0.78% (0.49%−1.18%) for the nirmatrelvir/ritonavir group and 6.54% (5.65%−7.52%) for the non-nirmatrelvir/ritonavir group; hazard ratio 0.11 (0.07−0.17; 89% relative risk reduction). Nirmatrelvir/ritonavir was effective in African American patients (hazard ratio, 0.35 [0.15−0.83]; 65% relative risk reduction). Relative risk reductions were comparable with overall results across ages and among vaccinated patients. Conclusions: Real-world nirmatrelvir/ritonavir effectiveness against hospitalization during the Omicron era supports EPIC-HR efficacy among high-risk patients. Future research should confirm these early realworld results and address limitations.

Competing Interests All authors are employees of Pfizer Inc and may hold stock or stock options. Data Sharing Statement Upon request, and subject to review, Pfizer will provide the summary data that support the findings of this study.

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