Patient-Reported Outcomes in COVID-19 Treatment with Monoclonal Antibodies Reveal Benefits in Return to Usual Activities

Abstract

Introduction: This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life.

Methods: We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active.

Results: In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively).

Conclusions: mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs.

Clinicaltrials: GOV: Registration number, NCT04425629; Submission date June 11, 2020.

Keywords: COVID-19; Monoclonal antibodies; Patient-reported outcomes; Quality of life; SARS-CoV-2; Symptoms.

Fig. 1

Time to sustained symptoms resolution for a ≥ 2 and b ≥ 3 consecutive days by treatment group. CAS + IMD casirivimab plus imdevimab, CI confidence interval, HR hazard ratio

Fig. 2

Time to return to usual health for a ≥ 1, b ≥ 2, and c ≥ 3 consecutive days. CAS + IMD casirivimab plus imdevimab, CI confidence interval, HR hazard ratio

Fig. 3

Time to return to usual activities for a ≥ 1, b ≥ 2, and c ≥ 3 consecutive days. CAS + IMD casirivimab plus imdevimab, CI confidence interval, HR hazard ratio

Fig. 4

Proportion of patients with improvement or worsening in each item of the EQ-5D-5L by treatment group in the PRO analysis set: a mobility, b self-care, c usual activities, d pain/discomfort, and e anxiety/depression. CAS + IMD casirivimab plus imdevimab, EQ-5D-5L EuroQol 5 Dimension 5 Level, PRO patient-reported outcome

Fig. 4

Proportion of patients with improvement or worsening in each item of the EQ-5D-5L by treatment group in the PRO analysis set: a mobility, b self-care, c usual activities, d pain/discomfort, and e anxiety/depression. CAS + IMD casirivimab plus imdevimab, EQ-5D-5L EuroQol 5 Dimension 5 Level, PRO patient-reported outcome

Fig. 5

LS mean change from baseline in EQ-5D VAS by treatment group* in the PRO analysis set. *The LS mean change from baseline in EQ-5D VAS was assessed using a mixed model for repeated measures that assumed an autoregressive order (1) covariance structure for within-subject repeated measurements. CAS + IMD casirivimab plus imdevimab, CI confidence interval, EQ-5D VAS EuroQol 5 Dimension visual analog scale, LS least squares, PRO patient-reported outcome