To date, there has yet to be established clear clinical, imaging, pathological, or immunological criteria to mark the transition from relapse-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS). In a recent study published in Neurology, a research team called for effective tools to enable the earlier identification of SPMS so that, when used together with available therapies, they could lead to improved long-term outcomes in patients with the disease.

According to the study investigators, emerging research suggested SPMS and RRMS “are part of a disease continuum with an indistinct boundary.” What’s less clear, however, are the underlying mechanisms involved in the transition from RRMS to SPMS.

Some research indicated that the transition may be associated with cortical demyelination and diffuse white matter injury, as these variables tend to increase with duration of RRMS.


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The study researchers emphasized that the conversion of the relapsing-remitting condition to a secondary progressive disease is clear evidence of the progression of disability. Additionally, therapies aimed to reduce the progression of disability in RRMS have not historically been proven effective in patients with SPMS, at least until recently.

The ORATORIO trial (ClinicalTrials.gov Identifier: NCT01194570), which evaluated monoclonal antibody ocrelizumab, is currently the only clinical trial that has met its primary efficacy endpoint of reducing confirmed disability progression in patients with primary progressive multiple sclerosis.

Inflammation is also a prime issue of importance in multiple sclerosis (MS), and research has focused intently on understanding its wide-reaching roles in the condition. Based on the current literature, the study researchers suggested that disease-modifying therapies (DMTs) are needed to target inflammation in the central nervous system (CNS), in addition to targeting acute peripherally mediated inflammation.

Given that recent studies supported the key role of chronic active lesions in disease progression, “the fact that these lesions are present in patients receiving DMTs that target peripherally mediated inflammation strengthens the notion that new treatments need to directly target CNS processes that contribute to progressive MS,” concluded the study researchers.

Disclosure: This clinical trial was supported by Novartis Pharma AG. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Cree BAC, Arnold DL, Chataway J, et al. Secondary progressive multiple sclerosis: New insights. Published online June 4, 2021. Neurology. doi:10.1212/WNL.0000000000012323