Treatment escalation leads to fewer relapses compared with switching to another moderately effective therapy

Background: Patients with multiple sclerosis who experience disease breakthrough often switch disease-modifying therapy (DMT). Objective: To compare treatment effectiveness of switch to highly effective DMT (heDMT) with switch to moderately effective DMT (meDMT) for patients who switch due to disease breakthrough defined as at least one relapse within 12 months of their treatment switch. Methods: We retrieved data from The Danish Multiple Sclerosis Registry on all relapsing-remitting MS patients with expanded disability status scale (EDSS) less than 6 who experienced disease breakthrough. We used propensity score matching to compare annualized relapse rates (ARRs), time to first confirmed relapse, time to first confirmed EDSS worsening and time to first confirmed EDSS improvement. Results: Each matched group comprised 404 patients. Median follow-up time was 3.2 years [interquartile range (IQR) 1.7–5.8]. ARRs were 0.22 (0.19–0.27) with heDMT and 0.32 (IQR 0.28–0.37) with meDMT; relapse rate ratio was 0.70 (95% CI 0.56–0.86; p = 0.001). Escalation to heDMT reduced the hazard of reaching a first relapse (HR 0.65; 95% CI 0.53–0.80; p < 0.001). We found no evidence of delayed disability worsening (HR 0.83; 95% CI 0.62–1.10; p = 0.20) and weak evidence of disability improvement (HR 1.33; 95% CI 1.00–1.76; p = 0.05) with heDMT. Conclusion: Switching to heDMT is associated with reduced ARR and delay of first relapse compared with switching to meDMT. Patients on DMT who experience relapses should escalate therapy to heDMT.