Real-World Effectiveness of Nirmatrelvir/Ritonavir on Coronavirus Disease 2019–Associated Hospitalization Prevention: A Population-based Cohort Study in the Province of Quebec, Canada

Abstract

Background The nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients. Methods This was a retrospective cohort study of SARS-CoV-2-infected outpatients between March 15 and October 15, 2022, using data from the Québec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared to infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk of COVID-19-associated hospitalization occurring within 30 days following the index date was assessed using a Poisson regression. Results A total of 8,402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced relative risk of hospitalization (RR: 0.31 [95%CI: 0.28; 0.36], NNT=13). The effect was more pronounced in outpatients with incomplete primary vaccination course (RR: 0.04 [95%CI: 0.03; 0.06], NNT=8), while no benefit was found in those with a complete primary vaccination course (RR: 0.93 [95%CI: 0.78; 1.08]). Subgroups analysis among high-risk outpatients with a primary vaccination course showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in relative risk of hospitalization in severely immunocompromised outpatients (RR: 0.66 [95%CI: 0.50; 0.89], NNT=16) and in high-risk outpatients aged 70 years and older (RR: 0.50 [95%CI: 0.34; 0.74], NNT=10) when the last dose of the vaccine was received at least six months ago. Conclusions Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.

Effectiveness of nirmatrelvir‐ritonavir on severe outcomes of COVID‐19 in the era of vaccination and Omicron: An updated meta‐analysis

“…Moreover, although NR was marketed for outpatient treatment of patients with mild to moderate disease at high risk of progression, some studies assessed the effect of NR on hospitalized patients 40,46,54,60–62 or did not exclude patients at standard risk for severe disease 35,36,38,40,43,45,57,61 . Nonetheless, our sensitivity analysis limiting the analysis to only the marketed patient population of high‐risk outpatients showed similar pooled RRs.…”

“…Of the 32 included studies, 14 offered effect estimates separated by vaccination status. Definition of fully vaccinated patients differed by study; some studies offered data for basic vaccination (two doses or one dose of the vaccine by Johnson & Johnson) and boosted patients (received ≥3 doses or the Johnson & Johnson vaccine + ≥1 booster dose), 20,34–36,43,45,55,57,58,61,63 others merged the group of basic vaccination and boosted patients (received ≥2 doses) 39,46,47 . These differences between studies may be due to differences in vaccination timelines across countries, with some countries having had earlier access to vaccination than others.…”

“…There was no evidence of publication bias for mortality, dose), 20,[34][35][36]43,45,55,57,58,61,63 others merged the group of basic vaccination and boosted patients (received ≥2 doses). 39,46,47 These differences between studies may be due to differences in vaccination timelines across countries, with some countries having had earlier access to vaccination than others.…”

“…The most heterogeneous results were observed for disease progression, with some studies reporting a statistically significant protective effect of NR, while other studies T A B L E 2 Comparison of the pooled risk ratios (RR) for the different outcomes, including sensitivity analyses and subgroup analysis. Included studies were 34,38,40,41,43,46,47,50,[52][53][54]58,[62][63][64][65][66] observed (nonsignificant) higher risk of progression with administration of NR.…”

Nirmatrelvir and ritonavir combination against COVID‐19 caused by omicron BA.2.2 in the elderly: A single‐center large observational study

“…Based on the randomized controlled study, numerous countries have granted emergency use authorization to nirmatrelvir-ritonavir for the management of COVID-19. Subsequently, a series of realworld studies [12][13][14][15][16][17] demonstrated the effectiveness of nirmatrelvir-ritonavir.…”