Symptom Alleviation/Resolution and Returns to Usual Health/Activities in Immunocompromised Adults with COVID-19 Treated with Nirmatrelvir-Ritonavir: Results from the EPIC-IC Trial

INTRODUCTION: EPIC-IC was a randomized, double-blind trial comparing the approved 5-day regimen of nirmatrelvir-ritonavir (NMV/r) vs. 10-day and 15-day NMV/r in immunocompromised individuals with mild-to-moderate COVID-19. We describe patient-reported global impressions of illness from EPIC-IC. METHODS: In EPIC-IC, 155 immunocompromised participants received 5-day, 10-day, or 15-day NMV/r (1:1:1). Participants completed the Global Impressions Questionnaire through week 24. Median times to first alleviation and resolution of symptoms and return to usual health and usual activities were estimated using Kaplan-Meier analyses for each treatment arm and post hoc subpopulations with severe vs. non-severe immunocompromise. Five-day arm times were compared vs. 10-day and 15-day arm times. RESULTS: Symptoms were alleviated after a median 6.0 (95% CI 4.0-9.0) days with 5-day NMV/r, similar to 9.0 (5.0-9.0) days with 10-day NMV/r (p = 0.627) and 10.0 (6.0-11.0) days with 15-day NMV/r (p = 0.528). Symptoms resolved after a median 16.0 (10.0-22.0) days with 5-day NMV/r, similar to 13.0 (9.0-14.0) days with 10-day (p = 0.140) and 13.0 (11.0-21.0) days with 15-day NMV/r (p = 0.471). In the severely immunocompromised subpopulation, symptoms resolved later with 5-day vs. 10-day NMV/r (p = 0.026). Participants returned to usual health after a median 11.0 (6.0-16.0) days with 5-day NMV/r, similar to 9.0 (6.0-13.0) days with 10-day (p = 0.319) and 10.0 (6.0-13.0) days with 15-day NMV/r (p = 0.218), and to usual activities after 10.0 (9.0-15.0) days with 5-day NMV/r, similar to 9.0 (6.0-10.0) days with 10-day (p = 0.102) and 9.0 (5.0-10.0) days with 15-day NMV/r (p = 0.190). CONCLUSIONS: Times to symptom alleviation/resolution and returns to usual health/activities were similar with 5-day vs. extended NMV/r and comparable to those in the EPIC-HR trial. Five-day treatment may be adequate for most immunocompromised individuals, while extended treatment might improve symptom resolution in those with severe immunocompromise; larger studies are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05438602.