Introduction: Worldwide, more than 2.5 million people suffer from Multiple Sclerosis (MS), which is a progressive degenerating disease of the central nervous system (CNS). At present, there is no definitive cure. Thus, available pharmacological therapies aim to reduce the disease activity by either suppressing or modulating the immune system. The humanised monoclonal antibody natalizumab (Tysabri™) was approved for the treatment of relapsing-remitting MS by the FDA and the EMA in 2006. Although, natalizumab is deemed to be highly effective, the treatment is associated with an increased risk of developing progressive multifocal encephalopathy (PML).

Methods: The aim of this systematic review was to investigate whether natalizumab is more effective and safer than alternative pharmacological therapies or placebo over a minimum follow-up period of 36 months with respect to annualised relapse rate, disability progression, quality of life (QoL) and number of serious adverse events (SAEs). A systematic literature search was conducted in four databases. The risk of bias (RoB) was assessed using the Cochrane RoB tool for randomised controlled studies and the ROBINS-I tool for non-randomised controlled trials. The quality of evidence was assessed using the GRADE-method (Grading of Recommendations, Assessment, Development and Evaluation).

Results: For the assessment of clinical effectiveness, three studies met the inclusion criteria. No significant differences regarding the annualised relapse rate and disability progression were found, when natalizumab was compared to fingolimod. A single trial investigated the patient-reported outcome quality of life. Yet, no significant difference was observed between the intervention group and a placebo control. For the assessment of safety, seven studies met the inclusion criteria. The proportion of patients suffering from SAEs ranged from 2.4% to 16.0%. Among them, infections and infestations (up to 4.0%), neoplasms (up to 2.0%) and hypersensitivity reactions (0.5% to 2.0%) were reported most frequently. In total, 35 cases of PML occurred.

Conclusion: Concerning clinical effectiveness and safety, the quality of evidence was low to very low. Thus, future research should provide more head-to-head RCTs comparing natalizumab with other disease modulating drugs along with a comprehensive documentation of adverse events.