Statistical Analysis
SAEs
ADVERSE EVENTS, REGRESSION, DISEASE
Descriptive and summary statistics for actual values and change from baseline for the primary safety outcome are shown where appropriate. Safety data was captured in real time, and assessments were focused on AEs (including study treatment tolerability assessments, laboratory evaluations, vital signs, and physical examination) and reported as such. The incidence rate of AEs was recorded by system organ class, severity, and by relationship to the study treatment. Overall summary of relevant AEs was reported if occurrence was greater than 10% of participants. Tolerability analysis was based on the number (%) of subjects who failed to complete the study due to adverse events. SAEs are reported using descriptive statistics.We assessed safety and tolerability of liothyronine in longitudinal analyses using mixed-effect regression models. Our initial analysis examined changes in serum thyroid function test scores and in measurements of EDSS, timed walking tests and health-related quality of life. Parameters of serum test scores, timed 25-foot walk test (T25FW) and nine-hole peg test (9HPT) were log-transformed to meet the normality assumption of the model. We further analyzed the changes in the main outcomes after adjusting for relevant characteristics (age, gender, BMI) as well as MS disease duration. We also considered the effect on the outcomes between the two different disease subtypes (relapsing and progressive MS), and we additionally fitted models after adjusting for the interaction of disease subtype with time. The correlations were examined by using analysis of variance (ANOVA) method. We performed subgroup analyses using similar models to describe the changes for each of the disease subtypes.We used a Wilcoxon Rank Sum test to determine if CSF proteins changed significantly over the course of the study. We used PANTHER and STRING databases to perform pathway enrichment analyses to determine the functional relevance of the changes in the proteome. No specific adjustments were made prior to the CSF analysis since the data analyzed was assessing protein changes at the individual level (within participant).