gms | German Medical Science

20. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin e. V.

Deutsches Netzwerk Evidenzbasierte Medizin e. V.

21. - 23.03.2019, Berlin

Natalizumab for the treatment of relapsing-remitting multiple sclerosis

Meeting Abstract

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  • Eva Fuchs - Ludwig-Boltzmann Institut, Health Technology Assessment, Österreich

EbM und Digitale Transformation in der Medizin. 20. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin. Berlin, 21.-23.03.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. Doc19ebmP-EG05-10

doi: 10.3205/19ebm084, urn:nbn:de:0183-19ebm0843

Veröffentlicht: 20. März 2019

© 2019 Fuchs.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Background/research question: 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 either by suppressing or by modulating the immune system.

The humanized monoclonal antibody Natalizumab (Tysabri) was approved for the treatment of relapsing-remitting multiple sclerosis by the FDA and the EMA in 2006. Although, Natalizumab has been shown to be highly effective, the treatment is associated with an increased risk of developing progressive multifocal encephalopathy (PML).

Methods: The aim of the systematic review was to investigate whether natalizumab is more effective and safer than alternative pharmacological therapies over a treatment period > 24 months with respect to annualized relapse rate, disability progression, QoL and number of serious adverse events (SAEs).

A systematic literature search was conducted in four databases (Medline, Embase, Toxline and Cochrane Central). The search was limited to prospective studies and articles published in English since 2011. Furthermore, the clinical trial registry ClinicalTrials.gov was assessed for ongoing clinical trials and observational studies. After deduplication, 303 citations were included. 35 articles were assessed in full-text, of which 7 were considered relevant.

Results: For the assessment of clinical effectiveness, three studies met the inclusion criteria. No significant differences regarding the annualized relapse rate and disability progression were found, if natalizumab was compared to fingolimod (rate ratio of 0.93 (95% CI. 0.74-1.17); p=0.53). A single trial investigated the patient-reported outcome QoL. 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%. Among them, infections and infestations (up to 4%), neoplasms (up to 2%) and hypersensitivity reactions (0.5% to 2%) were reported most frequently. In total, 35 cases of PML and 14 deaths occurred.

Conclusions: 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.

Competing interests: The author declares no conflict of interest.