Disease-modifying treatments for relapsing remitting multiple sclerosis, including rituximab. A health technology assessment.

Abstract

Key message We have systematically collected and reviewed the evidence for clinical effectiveness and general safety issues for disease modifying treatments for relapsing remitting multiple sclerosis, synthesised evidence from randomised controlled trials and non-randomised registry-based studies using network meta-regression, and carefully interpreted the findings. We included rituximab in our analysis as it is used off-label for the treatment of patients with RRMS, even though it does not hold marketing authorisation for RRMS. We included 35 randomised controlled trials and 11 non-randomised registry-based studies, with a total of almost 30 000 patients. We compared estimates of our predefined outcomes from meta-analysis of randomised controlled trials, of non-randomised registry-based studies, the network meta-regression, and other network meta-analytical models, and judged that the estimates are mutually consistent in most cases, and that where there is inconsistency, it could be explained. Based on the available evidence and the meta-analysis used: alemtuzumab is most likely to be the best treatment with respect to annual relapse rate; ocrelizumab and alemtuzumab are equally likely to be the best treatments with respect to risk of disability progression. Further, we estimate that rituximab is likely to have the lowest risk of serious adverse events and treatment withdrawal due to adverse events. However, the evidence for rituximab is from one small randomised trial of short duration and one non-randomised study, making this finding uncertain