Statistical analyses
HO lesions
REGRESSION
For the period 1 primary analysis, the TWA percent change from baseline in TLA For the period 2 primary analysis, the Wilcoxon signed-rank test was used to compare the number of new HO lesions as assessed by CT at week 56 (relative to the week 28 scan) with the number of new HO lesions at week 28 (relative to the baseline scan) in patients who crossed over from placebo to garetosmab. The estimate and 95% CI of the rate of new HO lesions at week 56 and that of the rate ratio (comparing period 2 to period 1) were based on a negative binomial model with repeated measures and using a generalized estimating equation. Safety outcomes were analyzed using descriptive statistics. To estimate the difference between period 2 and period 1 in total volume associated with new HO lesions, a MMRM model was implemented. The response variable was the total volume of new lesions at week 56 (relative to the week 28 scan) and at week 28 (relative to the baseline scan). The model included visit (week 28 and week 56) and the total volume by CT at baseline as a covariate. An unstructured covariance was used to account for within-patient correlation between visits. LS mean of differences in total volume of new lesions and the corresponding 95% CI are provided for comparison for week 56 against week 28. Similar methods were implemented for the corresponding PET-related end points. For the proportion of patient-related end points, the number and percent of patients who responded at week 56 relative to week 28 are provided for the placebo/garetosmab group (COVID-19 mITT set). In general, the within-group comparison used a McNemar’s test in the placebo/garetosmab group. A logistic regression model with repeated measures was used to estimate the odds ratio and 95% CI to compare period 2 and period 1 using the GEE. The model included visit (week 28 and week 56) and the baseline total number of lesions by CT (or PET) as a covariate. An unstructured covariance was used to account for within-patient correlation between time points.