Predictors of early response to cladribine in mexican patients with multiple sclerosis: A real world multicenter...

Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. In Mexico, its impact is considerable, driven by functional impairments and cognitive decline. Cladribine, an oral immune reconstitution therapy, has demonstrated efficacy in relapsing MS. However, predictors of therapeutic response in real-world Latin American populations remain unclear.

To identify baseline clinical and radiological predictors of early non-response to cladribine in Mexican patients with MS, using NEDA-3 status at one year as the primary outcome.

We conducted a multicenter, observational, retrospective study from 2019 to 2024 involving 155 patients with relapsing-remitting MS (RRMS) treated with cladribine across 8 clinical centers in Mexico. Inclusion criteria included age ≥18 years, MS diagnosis based on McDonald criteria, ≥12 months of follow-up, and at least one cladribine dose. Data included demographics, prior treatments, MRI findings, EDSS, relapses, and adverse events The primary outcome was NEDA-3 status at one year. Univariable and multivariable logistic regression models were used to identify baseline predictors of response to cladribine.

Among the 155 RRMS patients the mean age was 36.9 ± 18.5 years, the mean disease duration was 7.6 (± 6.6) years, the median number of prior relapses was 3 (IQR 2-4), and the median baseline EDSS was 2.0 (IQR 1.0-3.0). Fifty-two patients (40.0%) were treatment-naïve. Based on NEDA-3, 95 (61.3%) patients achieved responder status at year 1. In the multivariable analysis, baseline cognitive decline was the only independent predictor of non-response to cladribine at one year (aOR 4.86 [95% CI 1.40-19.6]; p = 0.017). Adverse events were reported in 79 patients (51.0%), most commonly grade 1-2 lymphopenia; no serious adverse events required treatment withdrawal.

In this real-world Mexican cohort, cladribine demonstrated a favorable efficacy and safety profile. Baseline cognitive decline was the only independent predictor of non-response to cladribine in the multivariate analysis. These findings may support early treatment decision-making and patient stratification in Latin American populations with MS.