Health-related quality of life in immunocompromised adults with mild-moderate COVID-19 treated with nirmatrelvir-ritonavir: results from the randomized, double-blinded EPIC-IC trial.

Abstract

BACKGROUND: Little is known about health-related quality of life (HRQoL) in immunocompromised people during and after COVID-19 illness. We describe HRQoL outcomes from the EPIC-IC trial, which included participants with immunocompromise and mild–moderate COVID-19. METHODS: EPIC-IC was a randomized, double-blind trial. Participants were assigned 1:1:1 to 5-day, 10-day, or 15-day nirmatrelvir-ritonavir (NMV/r) and completed the SF-36 and EQ-5D-5L through Week (W)24. HRQoL was analyzed across and by treatment arms for the evaluable population (N = 150) and in post hoc subpopulations with severe (n = 57) and non-severe (n = 93) immunocompromise. Mixed-effects longitudinal models compared 5-day vs. 10-day or 15-day NMV/r. RESULTS: In the overall sample, mean baseline SF-36 domain scores (norm-based; mean = 50, SD = 10) ranged from 35.7 to 44.1, mean Physical Component Summary (PCS) score was 37.9, and mean Mental Component Summary (MCS) score was 41.5 – all substantially worse than cancer comparator norms and age-matched general population (AMGP) norms. Baseline mean EQ-5D-5L Index score was 0.65; participants reported problems with pain/discomfort (90% of participants), usual activities (73%), mobility (50%), anxiety/depression (48%), and self-care (29%). These proportions improved through Day (D)15 (change from baseline [CFB]: − 49%-points for pain/discomfort, − 38%-points usual activities, − 22%-points mobility, − 24%-points anxiety/depression, − 19%-points self-care) and then stabilized. From the earliest post-baseline assessment (EQ-5D-5L: D5, SF-36: D10), all overall-sample outcomes improved significantly (-5D-5p < 0.05), with all mean improvements exceeding published minimum important difference thresholds (SF-36: 2–4-point; EQ-5D-5L Index: 0.03–0.05-point). Mean EQ-5D-5L Index score surpassed AMGP norms from D5 and peaked at D15 (0.21-point CFB). Mean SF-36 outcomes improved through W12; PCS surpassed AMGP norms at W12, while MCS approached but remained below AMGP norms. Improvements were sustained through W24 (W24 CFB: PCS, 10-point; MCS, 8-point; EQ-5D-5L Index, 0.20-point). EQ-5D-5L improvements appeared similar across immunocompromised subpopulations, whereas SF-36 improvements appeared slower and smaller in severely vs. non-severely immunocompromised participants. No significant treatment-arm differences were observed, except lower D10 PCS scores among severely immunocompromised participants treated with 5-day vs. 10-day NMV/r (p = 0.03). CONCLUSION: Immunocompromised individuals with mild–moderate COVID-19 experienced various HRQoL decrements, followed by rapid improvements during treatment that were sustained through W24. Interpretation is limited by the absence of an untreated control group. CLINICAL TRIAL REGISTRATION: Clinical trial number: NCT05438602. Registry: ClinicalTrials.gov. Registration date: June 28, 2022. URL: https://clinicaltrials.gov/ct2/show/NCT05438602 .