Overall and patient-specific comparative effectiveness of dimethyl fumarate versus teriflunomide: A novel approach to precision medicine applied to the German NeuroTrans Data Multiple Sclerosis Registry.

Abstract

Background: Multiple sclerosis (MS) comparative effectiveness research needs to go beyond average treatment effects (ATEs) and post-host subgroup analyses.

Objective: This retrospective study assessed overall and patient-specific effects of dimethyl fumarate (DMF) versus teriflunomide (TERI) in patients with relapsing-remitting MS.

Methods: A novel precision medicine (PM) scoring approach leverages advanced machine learning methods and adjusts for imbalances in baseline characteristics between patients receiving different treatments. Using the German NeuroTransData registry, we implemented and internally validated different scoring systems to distinguish patient-specific effects of DMF relative to TERI based on annualized relapse rates, time to first relapse, and time to confirmed disease progression.

Results: Among 2791 patients, there was superior ATE of DMF versus TERI for the two relapse-related endpoints (p = 0.037 and 0.018). Low to moderate signals of treatment effect heterogeneity were detected according to individualized scores. A MS patient subgroup was identified for whom DMF was more effective than TERI (p = 0.013): older (45 versus 38 years), longer MS duration (110 versus 50 months), not newly diagnosed (74% versus 40%), and no prior glatiramer acetate usage (35% versus 5%).

Conclusion: The implemented approach can disentangle prognostic differences from treatment effect heterogeneity and provide unbiased patient-specific profiling of comparative effectiveness based on real-world data.