An Italian study showed that long-term disability outcomes were more favourable with a strategy of early intensive treatment (EIT) than with moderate-efficacy treatment followed by escalation to higher-efficacy treatment (ESC). The difference in effect tended to increase over time even though patients in the ESC group escalated to a higher-efficacy disease-modifying treatment (DMT).

High-efficacy DMTs for relapsing-remitting MS (RRMS) are consistently more effective in reducing disease activity than traditional first-line therapies. However, there is no consensus on how aggressively and timely to treat RRMS patients. The most frequently used treatment strategy in clinical practice is based on the principle of escalation, as opposed to EIT.

Italian researchers evaluated disability in a large cohort of RRMS patients (n=2,652) stratified according to the applied treatment strategy (EIT or ESC). These patients had to have a ≥5-year follow-up and ≥3 visits after start of DMT, and a first visit within 3 years from disease onset. The EIT group included patients who received fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, or cladribine as their first DMT. Patients in the ESC group received a high-efficacy DMT after ≥1 year of treatment with one of the interferons, glatiramer acetate, azathioprine, teriflunomide, or dimethyl fumarate. Patients from both groups were paired 1:1 based on propensity score matching, resulting in 365 pairs. The median follow-up after initiation of the first DMT was 8.5 years. All patients in the ESC group switched to a higher-efficacy DMT after a median time of 5.1 years.

Estimated baseline Expanded Disability Status Scale (EDSS) did not differ significantly; 2.52 in the ESC group and 2.45 in the EIT group. Mean change in EDSS was significantly higher in the ESC group (P<0.02) after every subsequent 12-month interval. Mean change in estimated EDSS difference between the groups increased from 0.1 (95% CI 0.01–0.19; P=0.03) at 1 year, to 0.30 (95% CI 0.07-0.53; P=0.009) at 5 years, and to 0.67 (95% CI 0.31-1.03; P=0.0003) at 10 years.

The ever-increasing difference in treatment effects between groups may be explained, according to the authors, by the more potent effect on disability progression of the high-efficacy DMTs during the first years of treatment, or by the longer exposure. The authors added that the long-term safety risks of EIT should be further investigated.


  1. Iaffaldano P, et al. MSVIRTUAL2020, Abstract PS01.04.