Redefining Acute Relapses in Multiple Sclerosis: Implications for Phase 3 Clinical Trials and Treatment Algorithms

Abstract

Relapses in multiple sclerosis are defined as periods of clinical worsening and radiological progression. Magnetic resonance imaging data, however, are not always supportive of "clinical worsening," and clinical symptoms of worsening may not always be present in cases of acute relapse. In the pharmaceutical domain, this discordance between "clinical worsening" and "radiological progression" has never been fully elucidated, and no Phase 3 clinical study has addressed this conundrum. Thus, the true number of acute relapse cases enrolled in Phase 3 clinical studies remains unclear. Breach of the blood-brain barrier solely, as determined by magnetic resonance imaging, may be more a more accurate definition of an acute relapse in multiple sclerosis. Increasingly, magnetic resonance imaging data push the boundaries of science and carry significant advantages in sensitivity, data storage, retrieval, and unbiased analyses, if warranted retrospectively. Magnetic resonance imaging data can also be standardized, shared, and exploited by pharmaceutical companies to develop more effective drugs and therapeutic endpoints. Neurology is awakening to big data concepts and how such concepts are evolving the field. Magnetic resonance imaging data is one of the pillars of this evolution. In this commentary, the author reviews the current standard of determining acute relapse in both clinical practice and clinical research, and discusses its limitations. The author then proposes a more modern definition of acute relapse in multiple sclerosis and includes a supportive discussion on the current and emerging roles magnetic resonance imaging and "big data" are playing in the prevention, diagnosis, and treatment of multiple sclerosis.

Keywords: MRI; MS; Multiple sclerosis; acute relapse; big data; blood brain barrier; imaging; magnetic resonance imaging.