PURPOSE OF REVIEW: Multiple sclerosis (MS) is an immune-mediated disorder that 
affects the central nervous system (CNS), often first affecting people in early 
adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at 
disease onset, a substantial proportion later develop chronic progression, 
termed secondary progressive MS (SPMS). Approximately 10% of MS patients 
experience chronic progression from disease onset, termed primary progressive 
multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) 
options exist for relapsing forms of this disease, DMT options are few for 
progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, 
review major clinical trials aimed at progressive MS, and delineate potential 
strategies in the management of progressive MS.
RECENT FINDINGS: In 2017, the first DMT for PPMS, the B lymphocyte-depleting 
monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week 
confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a 
selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% 
versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients 
in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic 
acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS 
patients. Reasons now exist for optimism in the search for DMTs for progressive 
MS. It remains a challenge to identify outcome measures that accurately reflect 
the underlying pathology in progressive MS, which is less inflammatory and more 
degenerative than RRMS.