Clinical management of multiple sclerosis and neuromyelitis optica with therapeutic monoclonal antibodies: approved therapies and emerging candidates

Abstract

Therapeutic monoclonal antibodies (mAbs) are a relatively novel class of drugs that has substantially advanced immunotherapy for patients with multiple sclerosis. The advantage of these agents is that they bind specifically and exclusively to predetermined proteins or cells. Natalizumab was the first mAb in neurology to obtain approval. It is also considered one of the most potent options for annualized relapse rate reduction among available therapeutic options. Alemtuzumab is currently also approved in several countries. Several mAbs have been tested in clinical studies in multiple sclerosis. Here, we review the history of drug development of therapeutic mAbs and their classification. Furthermore, we outline the putative mechanisms of action, clinical evidence and safety of approved mAbs and those in different stages of clinical development in multiple sclerosis and neuromyelitis optica.

Keywords:

• monoclonal antibodies
• MS
• multiple sclerosis
• pharmacology
• therapies

Financial & competing interests disclosure

O Stuve serves on the editorial boards of JAMA Neurology, Multiple Sclerosis Journal and Therapeutic Advances in Neurological Disorders. He has received grant support from Teva Pharmaceuticals and Opexa Therapeutics. B Kieseier has received honoraria for lecturing, travel expenses for attending meetings and financial support for research from Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis and Teva and has served on the editorial boards of Journal of Neuroinflammation, European Journal of Medical Research and Current Medical Literature – Multiple Sclerosis. H Hartung has received honoraria for consulting and speaking, with approval by the Rector of Heinrich Heine University, from Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis and Teva, and has served on the editorial boards of Annals of Neurology, Current Opinion in Neurology and Therapeutic Advances in Neurological Disorders. He was a coinvestigator in the two Phase III trials CARE-MS I and CARE-MS II. Genzyme, from which all authors have received honoraria, has financial interests in alemtuzumab. B Hemmer has received compensation for serving as a scientific advisor and speaker for Hoffmann la Roche, Merck Serono, Biogen Idec, Novartis and Bayer. He serves as a consultant for Gerson Lehrman Group. He has received grant support for research projects from Novartis, Biogen Idec, Merck Serono, Bayer, Metanomics, Protagen AG, Roche, 5Prime, Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF) and Hertie Foundation. The authors have 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.

Key issues

• Therapeutic monoclonal antibodies (mAbs) are molecule specific.

• Therapeutic mAbs are sometimes cell lineage specific.

• Modern manufacturing methods have made recombinant mAbs less immunogenic.

• The effects and side effects of many therapeutic mAbs have enhanced our understanding of human autoimmune disease.

Notes