Better long-term disability outcomes in MS patients who are ‘early starters’ on high-efficacy therapies show that it is time to think the traditional escalation approach, Australian neurologists say.

Patients who started induction therapy within two years of disease onset had an average of one step difference in disability (Expanded Disability Status Scale, EDSS score) compared with those who started 4–6 years after disease onset, a retrospective registry-based study of patients with relapsing-remitting MS has found.

Led by Dr Anna He of Clinical Outcomes Research (CORe) Unit at Melbourne University, the study analysed data from two registries (MSBase and the Swedish MS registry) for adult patients who started high-efficacy therapies early (within two years of disease onset, n=213) or late (4–6 years after disease onset; n=253).

The patients were relatively young  (mean 31 years at disease onset) and the therapies included rituximab, ocrelizumab, mitoxantrone, alemtuzumab, and natalizumab.

At baseline the mean EDSS score was 2.2. In the sixth year after disease onset, the mean EDSS score was 2·2 in the early treatment group compared with 2·9 in the late group (p<0·0001). After adjusting for proportion of time on any disease-modifying therapy the average difference between groups in EDSS scores remained at 0·98 across the 6–10 year follow-up period.

The study investigators said the magnitude of disability prevented by earlier treatment was statistically and clinically significant and should lead to a rethink in traditional escalation approach with high efficacy therapies only started after unsuccessful treatment with first-line disease modifying therapies.

“High-efficacy immunotherapies provide the most benefit to patients with active relapsing-remitting multiple sclerosis when started without delay, early after first clinical presentation of MS,” they write in Lancet Neurology.

“We propose that highly potent therapies should be considered as a first-line choice in these patients. Accurate and timely identification of patients in the greatest need of an aggressive therapeutic approach is a subject of our future research.

This conclusion was supported in an accompanying commentary article by Dr Massimo Fillipi and Dr Maria Roccaab of the Institute of Experimental Neurology, Milan, who said the findings backed those of a recent real-life study that found that disability after five years was lower in patients starting high-efficacy treatment (alemtuzumab or natalizumab) than in those starting escalation treatment such as interferons, glatiramer acetate, dimethyl fumarate, fingolimod, or teriflunomide.

“Taken together, these two studies encourage a reappraisal of treatment algorithms in patients with multiple sclerosis,” they wrote.

“Overall, the evidence suggests that in multiple sclerosis there might be a short and early window of therapeutic opportunity in which the biology of disease can be substantially modified to affect long-term clinical outcomes.”