Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada
Kevin L Schwartz, J Wang, M Tadrous, B J Langford, N Daneman, V Leung, T Gomes, L Friedman, P Daley, K A Brown
doi:10.1101/2022.11.03.22281881
Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease. .
References
Agrawal, Bedston, Mccowan, Oke, Patterson et al., Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales, Lancet
Arbel, Sagy, Hoshen, Battat, Lavie et al., Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge, N Engl J Med
Austin, Stuart, Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies, Stat Med
Chung, He, Nasreen, Sundaram, Buchan et al., Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study, BMJ
Cole, Hernán, Constructing inverse probability weights for marginal structural models, Am J Epidemiol
Ganatra, Dani, Ahmad, Kumar, Shah et al., Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019 (COVID-19), Clin Infect Dis
Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med
Heilmann, Costacurta, Moghadasi, Ye, Pavan et al., SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376, Sci Transl Med
Komorowski, Evidence-based recommendations on the use of nirmatrelvir/ritonavir (Paxlovid) for adults in Ontario
Levy, 'brien, Sellors, Grootendorst, Willison, Coding accuracy of administrative drug claims in the Ontario Drug Benefit database, Can J Clin Pharmacol
Marzolini, Kuritzkes, Marra, Boyle, Gibbons et al., Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions, Ann Intern Med
Najjar-Debbiny, Gronich, Weber, Khoury, Amar et al., Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients, Clin Infect Dis
Nirmatrelvir/Ritonavir, (Paxlovid): What Prescribers and Pharmacists Need to Know Ontario COVID-19 Drugs and Biologics Clinical Practice Guidelines Working Group on behalf of the Ontario COVID-19, Science Advisory Table and University of Waterloo School of Pharmacy Version,
doi:10.47326/ocsat.2022.03.58.1.0Suissa, Immortal time bias in pharmaco-epidemiology, Am J Epidemiol
Takashita, Kinoshita, Yamayoshi, Sakai-Tagawa, Fujisaki et al., Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2, N Engl J Med
Ulloa, Buchan, Daneman, Brown, Estimates of SARS-CoV-2 Omicron Variant Severity in Ontario, Canada, JAMA
Xu, Ross, Raebel, Shetterly, Blanchette et al., Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals, Value Health
Yip, Lui, Lai, Wong, Tse et al., Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients, Clin Infect Dis [Internet
Zheng, Ma, Wang, Chen, Zhou et al., Efficacy and safety of Paxlovid for COVID-19:a meta-analysis, J Infect
{ 'institution': [{'name': 'medRxiv'}],
'indexed': {'date-parts': [[2022, 11, 6]], 'date-time': '2022-11-06T04:53:29Z', 'timestamp': 1667710409073},
'posted': {'date-parts': [[2022, 11, 5]]},
'group-title': 'Infectious Diseases (except HIV/AIDS)',
'reference-count': 0,
'publisher': 'Cold Spring Harbor Laboratory',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'accepted': {'date-parts': [[2022, 11, 5]]},
'abstract': '<jats:p>Background: Our objective was to evaluate the real world effectiveness of '
'nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants '
'predominate. Methods: We conducted a population based cohort study in Ontario, Canada '
'including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between '
'4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed '
'patients and measured the primary outcome of hospitalization or death from COVID-19, and a '
'secondary outcome of death 1-30 days. We used weighted logistic regression to calculate '
'weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of '
'treatment weighting (IPTW) to control for confounding. Results: The final cohort included '
'177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The '
'groups were well balanced with respect to demographic and clinical characteristics after '
'applying stabilized IPTW. Hospitalization or death within 30 days was lower in the '
'nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR '
'0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also '
'significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat '
'to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across '
'strata of age, DDIs, vaccination status, and comorbidities. Interpretation: '
'Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and '
'death from COVID-19 in this observational study, supporting ongoing use of this therapeutic '
'to treat patients with mild COVID-19 at risk for severe disease.</jats:p>',
'DOI': '10.1101/2022.11.03.22281881',
'type': 'posted-content',
'created': {'date-parts': [[2022, 11, 6]], 'date-time': '2022-11-06T02:15:10Z', 'timestamp': 1667700910000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort '
'study in Ontario, Canada',
'prefix': '10.1101',
'author': [ {'given': 'Kevin L', 'family': 'Schwartz', 'sequence': 'first', 'affiliation': []},
{'given': 'John', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mina', 'family': 'Tadrous', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bradley J', 'family': 'Langford', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nick', 'family': 'Daneman', 'sequence': 'additional', 'affiliation': []},
{'given': 'Valerie', 'family': 'Leung', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tara', 'family': 'Gomes', 'sequence': 'additional', 'affiliation': []},
{'given': 'Lindsay', 'family': 'Friedman', 'sequence': 'additional', 'affiliation': []},
{'given': 'Peter', 'family': 'Daley', 'sequence': 'additional', 'affiliation': []},
{'given': 'Kevin A', 'family': 'Brown', 'sequence': 'additional', 'affiliation': []}],
'member': '246',
'container-title': [],
'original-title': [],
'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2022.11.03.22281881',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 11, 6]],
'date-time': '2022-11-06T02:15:10Z',
'timestamp': 1667700910000},
'score': 1,
'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2022.11.03.22281881'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 11, 5]]},
'references-count': 0,
'URL': 'http://dx.doi.org/10.1101/2022.11.03.22281881',
'relation': {},
'published': {'date-parts': [[2022, 11, 5]]},
'subtype': 'preprint'}
