Patient-Reported Outcomes of Nirmatrelvir Treatment for High-Risk, Nonhospitalized Adults With Symptomatic COVID-19

Background Nirmatrelvir/ritonavir (NMV/r) is an antiviral treatment for COVID-19. We describe patient-reported outcomes (PROs) with NMV/r in nonhospitalized adults with COVID-19 at high risk of severe disease. Methods In a phase 2/3 double-blind study, high-risk adults with SARS-CoV-2 and ≤5 days of symptoms were randomized 1:1 to receive NMV/r or placebo twice daily for 5 days. Patients recorded responses to 3 Global Impression Questions (GIQ) daily through Day 28 to assess return to usual health, return to usual activities, and overall severity of COVID-19‒related symptoms. The COVID-19‒specific Work Productivity and Activity Impairment Questionnaire (WPAI-COVID-19) and EuroQol Quality of Life 5-dimension 5-level scale (EQ-5D-5L) were completed at specified visits through Week 24. Results Compared with placebo, patients receiving NMV/r had a significant 3-day reduction in median time to return to usual health (hazard ratio [HR], 1.3; 95% CI, 1.2‒1.4; P<0.0001), 1-day reduction in median time to return to usual activities (HR, 1.2; 95% CI, 1.1‒1.4; P<0.0001), and significantly shorter GIQ times to sustained resolution of any overall symptoms (HR, 1.2; 95% CI, 1.1‒1.3; P=0.0002) and sustained alleviation of any overall symptoms (HR, 1.2; 95% CI, 1.1‒1.3; P<0.0001). There were no significant differences between treatment groups in the WPAI-COVID-19 or EQ-5D-5L results. Conclusions Patients receiving NMV/r for COVID-19 reported a reduced duration and severity of COVID-19 symptoms based on their global impression of overall symptom burden and quicker return to usual health and usual activities compared with those receiving placebo. Clinical Trial Information ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202