Multiple Sclerosis is a progressive, degenerating disease of the central nervous system (CNS), which affects more than 2.5 million people worldwide. The monoclonal antibody natalizumab (TysabriTM) has been approved by the European Medicines Agency in 2006. Yet, the treatment is associated with an increased risk of developing progressive multifocal encephalopathy (PML). The aim of the systematic review was to investigate whether natalizumab is more effective and safer than alternative pharmacological therapies or placebo over a prolonged period (≥ 36 months) with respect to annualised relapse rate (ARR), disability progression, quality of life and number of serious adverse events (SAEs).

A systematic literature search was conducted considering randomized controlled trials (no restriction in length) and prospective, non-randomized controlled trials. In terms of safety, prospective single arm studies were additionally included. The risk of bias (RoB) was assessed using the Cochrane RoB tool (RCT), the ROBINS-I tool (NRCT) and the Institute of Health Economics quality appraisal checklist (IHE-20) for case series (single-arm studies). The quality of evidence was determined using the GRADE-method (Grading of Recommendations, Assessment, Development and Evaluation).

For the assessment of clinical effectiveness, three studies (one RCT and two NRCTs) met the inclusion criteria. No significant differences regarding the ARR and disability progression were detected, if natalizumab was compared to an alternative treatment with fingolimod. Yet, if compared to placebo or a group of natalizumab interrupters, a 70 percent reduction in the ARR was observed. For the assessment of safety, seven studies met the inclusion criteria. The proportion of patients suffering from SAEs ranged from 2.4 percent to 16.0 percent. In total, 35 cases of PML occurred. The results were supported by a very low quality of evidence.

Future research should provide more head-to-head RCTs comparing natalizumab with other disease modulating drugs along with a comprehensive documentation of adverse events.