Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, with recent estimates of around 1 million people living with MS in the US. 1 In many countries, MS is a leading cause of disability among young adults, second only to trauma. 2 Clinically, neurologic worsening (ie, disability) in MS can occur in the relapsing-remitting (RRMS) phase of disease due to incomplete recovery from neuroinflammatory relapses. However, in the 15% of patients with a progressive course from onset (PPMS), and in those with RRMS who transition to a secondary progressive phenotype (SPMS), neurologic worsening follows a slowly progressive pattern. 3 A progressive disease course—either PPMS at onset or transitioning to SPMS—is the dominant factor affecting MS-related neurologic disability accumulation. In particular, epidemiologic studies have shown that, in the absence of transitioning to a progressive disease course, < 5% of individuals with MS will accumulate sufficient disability to necessitate use of a cane for ambulation. 4-6 Therefore, developing disease modifying therapies (DMTs) that are highly effective at slowing or stopping the gradual accumulation of neurologic disability in progressive MS represent a critical unmet need.
The Future of Progressive Multiple Sclerosis Therapies
Chris Hollen is Multiple Sclerosis Fellow and Rebecca Spain is a Neurologist and the Associate Director of Clinical Affairs for the MSCoE-West, both at the VA Portland Health Care System in Oregon. Mateo Paz Soldán is a Neurologist and the Clinical Director of the MSCoE-West Regional Program at the VA Salt Lake City Health Care System in Utah. John Rinker is a Neurologist and the Clinic Director of the MS Clinic at the Birmingham VA Medical Center in Alabama.
Correspondence: Chris Hollen ([email protected])
The authors report no actual or potential conflicts of interest with regard to this article.
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
Introduction: Multiple sclerosis (MS) affects more than a million people in the US. A considerable portion of these patients either begin with primary progressive disease or eventually transition to secondary progressive MS. A progressive disease course is the most critical factor affecting disability accumulation. The relatively recent development of treatments for relapsing multiple sclerosis has had a profound impact on the disease course for many with MS. Unfortunately, therapies for progressive MS have not had the same degree of advancement in general. New insights into the pathophysiology of progressive MS may lead to new treatments.
Observations: In this review, we identify some of the significant challenges encountered in the development of therapies for progressive MS, assess the evidence for use of currently approved therapies for patients with progressive MS, identify some of the current therapies in development from progressive MS, and consider the role for discontinuing therapy in certain patients.
Conclusions: Developing effective disease modifying therapies that slow or stop the gradual accumulation of neurologic disability in progressive MS represents a critical unmet need. As the understanding of the inflammatory and neurodegenerative aspects of MS are better elucidated there may be opportunity for advancement in the treatment of progressive MS.