PURPOSE OF REVIEW: The purpose of this study is to highlight the pathological 
features and clinical aspects of progressive multiple sclerosis (PMS) and also 
the results of clinical trial experience to date and review ongoing clinical 
trials and prospective new treatment options. This study will explain the 
challenges of clinical trial design in PMS.
RECENT FINDINGS: Multiple sclerosis (MS) has been identified as a chronic immune 
mediated disease, and the progressive phase of the disease appears to have 
significant neurodegenerative mechanisms. The classification of the course of 
PMS has been reorganized into categories of active vs. inactive inflammatory 
disease and the presence vs. absence of gradual disease progression. This 
differentiation allows clearer conceptualization of PMS and possibly even more 
efficient recruitment of PMS patients into clinical trials. Clinical trial 
experience to date in PMS has been negative with anti-inflammatory medications 
used in relapsing MS. Simvastatin was recently tested in a phase II trial and 
showed a 43% reduction of annualized atrophy progression in secondary 
progressive MS. Ongoing PMS trials are currently being conducted with the 
phosphodiesterase inhibitor ibudilast, S1P modulator siponimod and anti-B-cell 
therapy ocrelizumab. Several efforts for development of outcome measures in PMS 
are ongoing.
SUMMARY: PMS represents a significant challenge, as the pathogenesis of the 
disease is not well understood, no validated outcome metrics have been 
established and clinical trial experience to date has been disappointing. 
Advances in the understanding of the disease and lessons learned in previous 
clinical trials are paving the way for successful development of 
disease-modifying agents for this disease.