Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk

Abstract

Background We aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in highly vulnerable SARS-CoV-2 patients using a retrospective cohort study design. Methods The impact of each drug was determined via comparisons with age-matched control groups of SARS-CoV-2-positive patients who did not receive oral antiviral therapy. Results Administration of molnupiravir significantly reduced the risk of hospitalization (Odds Ratio [OR] = 0.40, p < 0.001) and death (OR = 0.31, p < 0.001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR = 0.31, p < 0.001) and death (OR = 0.28, p < 0.001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence. Conclusions Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations.

Oral antivirals for COVID-19 among patients with cancer

“…The RCT data supporting the e cacy of Lagevrio® among unvaccinated patients were weaker than those of Paxlovid®, and its EUA was supported by a marginal vote. A recent registry-based study claimed a signi cant bene t, almost similar to Paxlovid®, especially among elderly patients, even after adjustment for vaccination status and time from last vaccine dose [7]. Nevertheless, the PANORAMIC clinical trial [29], where > 96% of patients were fully vaccinated, showed no difference in clinical outcomes between molnupiravir and usual care alone, similar to the results of a recent systematic review and metaanalysis [16].…”

“…Both nirmatrelvir/ritonavir (Paxlovid®) and molnupiravir (Lagevrio®) are FDA-approved for the treatment of COVID-19 based on the results of two randomized clinical trials (RCTs) from previous phases of the pandemic [4,5], with the latter being under emergency use authorization. Additionally, their effectiveness was con rmed in large retrospective registries, which included small proportions of immunosuppressed patients [6,7]. That being said, several groups [4,5,[8][9][10][11] have studied the bene cial role of those antivirals among eligible immunocompromised outpatients only, with relatively mixed results.…”

Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review

“…Nine studies (six peer-reviewed studies and three pre-prints) met all PICOTS criteria and were included in the SLR (Table 2 ) [ 29 – 37 ]. Two of the three pre-prints have subsequently been published as peer-reviewed articles [ 38 , 39 ]. The peer-reviewed version of Paraskevis et al .…”

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk COVID-19 patients in north west London: a retrospective cohort study

“…As with sotrovimab, real-world studies have assessed the effectiveness of other available treatments during periods when Omicron subvariants have been predominant. A study in Greece among patients aged ≥65 years reported that both molnupiravir and nirmatrelvir/ritonavir significantly reduced the risk of hospitalisation and death compared with no oral antiviral therapy 36. The study included a period when Omicron subvariants BA.1, BA.2 and BA.5 successively predominated (December 2021 to July 2022).…”