Risk factors for conversion to secondary progressive MS

To date, according to the Lublin definition, secondary progressive MS and its diagnosis are retrospective, based on a history of gradual EDSS worsening [1,2]. There are no clear metrics for sensitive and reliable identification of the transition from relapsing-remitting MS to secondary progressive MS available to assist neurologists in daily clinical practice.

In 2016, an objective definition of secondary progressive MS was proposed, based on the application of a mathematical algorithm to longitudinally recorded EDSS score evaluations in the MSBase platform [3]. Caution should be taken, because the way conversion is defined may affect the risk and protective factors eventually associated with the disease course transition. So far, no studies have evaluated the risk factors for conversion using different secondary progressive MS definitions.

In a large cohort of relapsing-remitting MS patients (n=19,318) extracted from the Italian MS Registry, two different definitions of secondary progressive MS were applied:

• Firstly, the date of conversion annotated in the database, which was based on the subjective judgement of the neurologists, was extracted;
• Secondly, a data-driven definition based on an EDSS increase, in the absence of a relapse, with a minimum EDSS ≥4 and pyramidal score ≥2 at time of conversion [4].

The risk of reaching the secondary progressive MS was assessed by using multivariate Cox proportional hazards models. A data-driven definition of secondary progressive MS seems to select a population more likely to be in the progressive phase of the disease in comparison to the diagnosis of the neurologist.

By using both the definitions, Dr Pietro Iaffaldano (University of Bari Aldo Moro, Italy) and colleagues confirmed that the most important risk factors for the transition of relapsing-remitting MS to secondary progressive MS are a multifocal onset, an older age of onset, and a higher number of relapses. Furthermore, they confirmed that the most important protective factor against the transition to secondary progressive MS is disease-modifying treatment exposure. “The higher the exposure, the lower the risk of progression”, he added.
After transition, disease-modifying treatment exposure does not have an impact on the risk of disability accrual. The major driver of disability accumulation in this phase of the disease are relapses. So, an accurate and less ambiguous secondary progressive MS definition is warranted to assist the neurologists and the scientific community in the efforts to find newer treatment strategies against progressive MS [4].

1. Lublin FD, Reingold SC. Neurology. 1996;46:907-11.
2. Lublin FD, et al. Neurology. 2014;83:278-86.
3. Lorscheider J, et al. Brain. 2016;139(Pt 9):2395-405.
4. Iaffaldano P, et al. ECTRIMS 2019, abstract 156.

Posted on 8 November 201925 March 2024