Treating multiple sclerosis with monoclonal antibodies: a 2010 update

Abstract

Treating multiple sclerosis (MS) with monoclonal antibodies (mAbs) has been marked by both progress and setbacks in the past 2 years, which are reviewed here. The natalizumab section of the article centers around progressive multifocal leukoencephalopathy (PML), and discusses PML risk in relation to treatment duration, bioassays for individual risk prediction, the concept of drug holidays, clinical course and treatment of PML, as well as safety-related regulatory actions. The rituximab section critically analyzes recent clinical trial results, discusses the clinical relevance of anti-idiotypic mAbs and makes a short excursion to neuromyelitis optica. Following this, the newer anti-CD20 mAbs ocrelizumab and ofatumumab, which are currently being tested in Phase II for MS, are reviewed and compared. The alemtuzumab section highlights novel data on mechanisms of action, potentially allowing individual risk prediction, and new results from the CAMMS223 trial, as well as the current status of the pivotal MS studies. The daclizumab section summarizes new open-label data, shedding more light on the adverse-effect profile of the drug in MS patients, and reports on its Phase III status. Subsequently, a failed ustekinumab trial and LY2127399 are reviewed. Taking into account late Phase II and III data on novel oral agents, the final section attempts to provide a detailed perspective on disease-modifying MS therapy in the medium term.

Keywords::

• alemtuzumab
• daclizumab
• LY2127399
• multiple sclerosis
• natalizumab
• ocrelizumab
• ofatumumab
• progressive multifocal leukoencephalopathy
• rituximab
• ustekinumab

Financial & competing interests disclosure

This work was supported by grant A-57 from Interdisziplinäres Zentrum für Klinische Forschung (IZKF) at the University of Würzburg, Germany. Mathias Buttmann received research support from Merck Serono and Teva/Sanofi-Aventis, and travel grants and lecture fees from Bayer Schering Pharma AG and Merck Serono. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.