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BACKGROUND Vascular comorbidity (VC) is associated with multiple sclerosis (MS) disease progression and visual dysfunction. The longitudinal effect of VC in people with secondary progressive MS (SPMS) is unclear. This study explored the impact of VC on standard clinical, MRI, and visual outcomes in people with SPMS enrolled in a clinical trial. METHODS Data were extracted from a 2-year randomized controlled trial (N = 51) testing the supplement lipoic acid in people with SPMS who underwent annual Expanded Disability Status Scales, Timed 25-Foot Walk tests, MRIs, visual acuity testing, and retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) thicknesses per optical coherence tomography (OCT). Post hoc linear mixed-effects regression analysis compared baseline and annualized outcomes between participants without VC (VC−) and with 1 or more VCs (VC+) (hypertension, dyslipidemia, obesity, diabetes, peripheral or cardiovascular disease, tobacco use). RESULTS The VC− (n = 19) and VC+ (n = 28) participants were similar in age, sex, and MS disease duration and had comparable MS disability, mobility, and brain atrophy at baseline and throughout the 2-year parent study. The VC+ participants had worse baseline visual acuity than those in the VC− group by 0.13 logMAR (P = .041). No significant differences were detected in RNFL or GCIPL baseline thickness or atrophy between groups. CONCLUSIONS In an SPMS cohort, VC had an inconsistent effect on standard clinical, MRI, and exploratory OCT outcomes, suggesting that the effect of VC may not be evident in smaller cohort studies. Using a more refined definition of VC in future, adequately powered investigations may help effectively elucidate and account for the interaction between vascular risk burden and MS disability.

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.