Various clinical and imaging factors, including age at onset of treatment, EDSS (Expanded Disability Status Scale) score, and the annualized relapse rate, may predict initial treatment failure in patients with recently diagnosed relapsing remitting multiple sclerosis (MS) published study results in multiple sclerosis and related disorders.
Treatment options for MS have changed significantly in recent years, and new and effective drugs are now approved for initial treatment. For this reason, it is important to better identify patients at risk of initial treatment failure. The aim of the current study was to identify predictive markers associated with failure of first-line therapy in patients with relapsing-remitting MS.
The researchers conducted a multicenter retrospective study (ClinicalTrials.gov Identifier: NCT02889965) that enrolled 863 patients (women, 73%; mean age 33.8 years) with a diagnosis of recurrent remitting MS from 3 major French tertiary MS centers. Of these, 185 patients had to be switched to second-line therapy, also known as highly effective therapy (HRT), while 678 patients continued on first-line therapy.
During a median follow-up of 5.3 years, treatment failure was reported in 23.5 percent of patients, including disease relapse (83%) and / or gadolinium-enhancing lesions (69%) in 95 percent of patients.
One of the most important basic characteristics associated with an increased risk of treatment failure is an age of less than 26 years at the start of initial treatment (hazard ratio) [HR]2.11; 95% CI, 1.45-3.07; P <0.001), EDSS score of at least 2 (HR 2.05; 95% CI 1.42-2.95; P <0.001), at least 2 relapses in the previous year (HR 1.44; 95% CI 1.01 -) 2.07; P = 0.044) and the presence of gadolinium-enhancing lesions (HR 1.32; 95% CI 0.90-1.95; P = 0.152). The type of initial 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 likelihood of switching to highly effective therapies was 65 percent higher in patients with 3 to 4 risk factors (HR 1.65; P = 0.006).
Data on EDSS were available for 464 patients at the start of the study and during the follow-up examination. The only factors associated with the increase in EDSS were age at initiation of treatment (HR 1.05 for each annual increase in age; P <0.001) and treatment failure (HR 4.72; P <0.001).
The study had several limitations, including the retrospective and observational design, the relatively small sample size, and the possible heterogeneity of data from three different centers.
“We suggest that younger patients with EDSS ≥ 2 and high annualized relapse rates and gadolinium-enhancing lesions should benefit from HRT as 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 on December 12, 2020. doi: 10.1016 / j.msard.2020.102686