Data abstraction
The titles and abstracts of studies retrieved during the searches were screened for duplicates by two independent reviewers (PB and PW). Potentially relevant full-texts were then screened according to our inclusion and exclusion criteria. The final included studies were then collated, and the two reviewers used standardized data extraction formats to extract the data. After extraction, both reviewers matched their data with each other and revisited papers where disagreements arose. Any discrepancies were resolved through discussion with other team members. The extracted data included the following: first author, study design, site of study, year of publication, language, number of patients receiving fingolimod, the values of variables If required data was missing, not reported in the paper, or reported in an unusual form, the corresponding authors of the respective papers were contacted for clarification. Supplementary material associated with the main paper was also explored in such cases.
Risk of Bias Assessment and Quality of Evidence
Two authors (PB and PW)individually assessed the methodological quality of RCTs using the Cochrane Collaboration tool for assessing the risk of bias. (23) (24)The criteria were selected a priori and included: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting(including reporting of all outcomes and specifying a primary outcome), and (7) other bias. The evaluated domains were judged as low risk, high risk, or unclear bias per established criteria. In the case of evaluation discrepancies, the authors discussed and came to an agreement.