Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system

Area of Science:

• Neurology
• Clinical Research
• Biostatistics

Background:

• Early identification of suboptimal responders in relapsing-remitting multiple sclerosis (RRMS) is crucial for preventing disability progression.
• Current treatment strategies may not adequately address the needs of all RRMS patients, necessitating improved methods for treatment adjustment.

Purpose of the Study:

• To develop and validate a dynamic score for guiding early decisions on switching from first- to second-line therapy in RRMS patients.
• To improve patient outcomes by enabling timely therapeutic interventions based on individual response.

Main Methods:

• Utilized time-dependent propensity scores (PS) from a large French cohort (12,823 RRMS patients).
• Constructed training and validation PS-matched cohorts to compare outcomes of patients switched to second-line treatment versus those maintained on first-line therapy.
• Employed a frailty Cox model to predict individual hazard ratios (iHRs) for relapse risk.

Main Results:

• In a validation cohort (iHR ≤ 0.69), 5-year relapse-free survival was 0.14 for the waiting group and 0.40 for the switched group.
• In a separate validation cohort (iHR > 0.69), 5-year relapse-free survival was 0.37 for the waiting group and 0.44 for the switched group.
• The dynamic score effectively differentiated patient groups with varying relapse risks.

Conclusions:

• The developed dynamic score can guide early treatment decisions in RRMS.
• An estimated one-third of RRMS patients could benefit from an earlier switch to second-line therapy to prevent relapses.
• This score offers a valuable tool for personalized treatment strategies in managing RRMS.