Background and Aims:

How aggressively and timely treat relapsing-remitting multiple sclerosis (RRMS) is still a matter of debate.

To evaluate long-term disability trajectories in RRMS patients treated with two different therapeutic strategies: early intensive treatment (EIT) or moderate-efficacy treatment followed by escalation to higher-efficacy DMT (ESC).

Methods:

RRMS patients with ≥5-year follow-up and ≥3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received, as first DMT natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine, mitoxantrone,. ESC group patients received the high efficacy DMT after ≥1 year of injectables DMTs, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS)-matched for characteristics at the first DMT. A longitudinal model for repeated measures was applied to evaluate the disability trajectories. To estimate the effect of early versus late start of high-efficacy DMT the mean annual EDSS changes were compared to baseline values (delta-EDSS) in EIT and ESC groups.

Results:

2,702 patients were included in our study cohort. After PS matching procedure 363 pairs were retained. The median (IQR) follow-up was 8.5 (6.5–11.7) years. The ESC strategy was associated with a faster EDSS increase over time in comparison to the EIT (p<0.02). The mean delta-EDSS differences between the two groups increased from 0.1 (0.01-0.19, p=0.03) at 1 year to 0.30 (0.07-0.53, p=0.009) at 5 years and to 0.67 (0.31-1.03, p=0.0003) at 10 years.

Conclusions:

Our findings indicate a higher effectiveness of EIT than ESC strategy in slowing disability worsening over time.