EFFECTS of CASIRIVIMAB + IMDEVIMAB on SYMPTOM OUTCOMES in OUTPATIENTS with COVID-19

ABSTRACT

Background: Symptoms reduction is a crucial outcome to be considered when testing novel treatments for COVID-19. The goal was to assess the impact of casirivimab+imdevimab (cas+imd) dose/exposure on the trajectory and resolution time of symptoms in outpatients with COVID-19. Methods: Analysis used data from the COV-2067 trial (NCT04425629). Cas+imd was administered intravenously (total dose 1.2 to 8 g). Symptoms data were collected using SE-C19, a patient-reported survey developed de novo to assess the symptomatic course of COVID-19. Based on patients' responses on SE-C19, a Rasch analysis was used to derive a latent score to infer their overall underlying symptom severity. A direct response model was fitted to the latent score-time data to quantify the effects of dose/exposure, demographic and clinical characteristics on latent symptom trajectory. Symptoms resolution time was defined as time from randomization to the 1st day during which the patient scored "no symptom". Several parametric models were tested as structural model, assuming a known distribution, eg, exponential or Weibull, for time to symptoms resolution data. Risk variables (eg, binary treatment or categorical dose levels, exposure metrics, baseline demographic, clinical, and biological characteristics) were tested as covariates using a proportional hazard model. Results: Results from the direct response model suggest that each dose, as compared to placebo, remarkably reduced IT50 (time taken to achieve half of the maximal response of reducing symptom) by ∼40%. By excluding data from placebo arm, none of the tested doses or predicted exposures, were significant covariates on any of the model parameters. Results from the parametric regression analysis further confirmed that cas+imd (HR=1.25) is a major factor shortening the symptoms resolution time in a dose-and exposure-independent manner. Males (HR=1.13) have a shorter symptoms resolution time. Older age (HR=0.991), higher BMI (HR=0.988), and more severe baseline symptoms (HR=0.783 for moderate and 0.589 for severe) significantly contribute to longer symptoms resolution time. Conclusion: Treatment with cas+imd (1.2 g or above), rapidly resolved symptoms in outpatients in a dose-and exposure-independent manner as indicated by a direct response model using derived latent score and further confirmed by a survival analysis using time to symptoms resolution. In addition, symptom severity, age, BMI, sex were major risk factors affecting the symptoms resolution time.