Escalating to medium- versus high-efficacy disease modifying therapy after low-efficacy treatment in relapsing remitting multiple sclerosis

BackgroundIn patients with relapsing remitting multiple sclerosis (RRMS) on low-efficacy disease modifying therapies (DMT), the optimal strategy on how to escalate treatment once needed, remains unknown.Methods:We studied RRMS patients on low-efficacy DMTs listed in the Swiss National Treatment Registry, who underwent escalation to either medium- or high-efficacy DMTs. Propensity score-based matching was applied using 12 clinically relevant variables. Both groups were also separately matched with control subjects who did not escalate therapy. Time to relapse and to disability worsening were evaluated using Cox proportional hazard models.Results:Of 1037 eligible patients, we 1:1 matched 450 MS patients who switched from low-efficacy to medium-efficacy (n = 225; 76.0% females, aged 42.4 +/- 9.9 years [mean +/- SD], median EDSS 3.0 [IQR 2-4]) or high-efficacy DMTs (n = 225; 72.4% females, aged 42.2 +/- 10.6 years, median EDSS 3.0 [IQR 2-4]). Escalation to high-efficacy DMTs was associated with lower hazards of relapses than medium-efficacy DMTs (HR = 0.67, 95% CI 0.47-0.95, p = .027) or control subjects (HR = 0.61, 95% CI 0.44-0.84, p = .003). By contrast, escalation from low to medium-efficacy DMTs did not alter the hazard for relapses when compared to controls (i.e. patients on low-efficacy DMT who did not escalate DMT during follow-up)Conclusion:Our nationwide registry analysis suggests that, once escalation from a low-efficacy DMT is indicated, switching directly to a high-efficacy treatment is superior to a stepwise escalation starting with a moderate-efficacy treatment. This study investigated two escalation strategies in patients with multiple sclerosis receiving low-efficacy treatment: Stepwise escalation to medium-efficacy treatment vs. direct escalation to high-efficacy treatment. It found that direct escalation to high-efficacy therapy is superior in preventing future relapses. It therefore advocates for a direct escalation to high-efficacy treatment once needed, in patients initially following an escalation approach by starting low-efficacy treatment. image