Predictive Markers of First-Line Treatment Failure in Patients with MS

Study researchers found several clinical and imaging factors that predicted first-line treatment failure in patients with recently diagnosed relapsing remitting MS.

Several clinical and imaging factors, including age at treatment initiation, Expanded Disability Status Scale (EDSS) score, and annualized relapse rate, can predict first-line treatment failure in patients with a recent diagnosis of relapsing remitting multiple sclerosis (MS), according to study results published in Multiple Sclerosis and Related Disorders.

The treatment options for MS have changed significantly in recent years and new and potent medications are now approved for first-line treatment. For this reason, it is critical to better identify patients at risk for first-line treatment failure. The objective of the current study was to identify predictive markers associated with failure of first-line therapy in patients with relapsing-remitting MS.

Researchers conducted a multicenter retrospective study ( Identifier: NCT02889965) that included 863 patients (women, 73%; mean age, 33.8 years) with a diagnosis of relapsing-remitting MS from 3 large tertiary French MS centers. Of these, 185 patients required treatment switch to a second-line therapy also labeled as a highly effective therapy (HET), while 678 patients maintained the first-line treatment.

During a mean follow-up of 5.3 years, treatment failure was reported in 23.5 percent of the patients, including disease relapse (83%) and/or gadolinium enhancing lesions (69%) in 95 percent of patients.

The main baseline characteristics associated with increased risk for treatment failure included an age of less than 26 years at first-line treatment initiation (hazard ratio [HR], 2.11; 95% CI, 1.45-3.07; P <.001), EDSS score of at least 2 (HR, 2.05; 95% CI, 1.42-2.95; P <.001), at least 2 relapses in the previous year (HR, 1.44; 95% CI, 1.01-2.07; P =.044), and the presence of  gadolinium enhancing lesions (HR, 1.32; 95% CI, 0.90-1.95; P =.152). The type of first-line treatment was not a significant predictor of treatment failure.

Compared to patients with no more than 2 of these risk factors for treatment failure, the probability of switching to highly effective therapies was 65 percent higher for those with 3 to 4 risk factors (HR, 1.65; P =.006). 

Data on EDSS at baseline and during the follow-up were available for 464 patients. The only factors associated with EDSS increase were age at treatment initiation (HR, 1.05 for each year increase in age; P <.001) and treatment failure (HR, 4.72; P <.001).

The study had several limitations, including its retrospective and observational design, relatively small sample size, and potential heterogeneity of the data from 3 different centers.

“We propose that younger patients with EDSS≥2 and high annualized relapse rate as well as gadolinium enhancing lesions, should benefit from HET as a FLT [first-line treatment],” concluded the study researchers.


Ayrignac X, Bigaut K, Pelletier J, et al. First line treatment failure: Predictive factors in a cohort of 863 relapsing remitting MS patients. Mult Scler Relat Disord. Published online December 12, 2020. doi:10.1016/j.msard.2020.102686