Escalation versus Early Initiation of Highly Effective Therapy in Relapsing-Remitting Multiple Sclerosis

September 2022

Guidelines for treatment strategies for relapsing-remitting multiple sclerosis (MS) most often recommend starting with a first-line low to moderately effective therapy and escalating to a highly effective disease-modifying therapy (DMT) when signs of disease progression are detected. An alternative strategy is to start with a highly effective DMT when there is already evidence of a high level of disease activity at diagnosis. Comparisons of the efficacy of treatment strategies are lacking.

The objective of a recent study was to compare outcomes for patients at the national level in countries with different strategies for DMT use in patients with MS. The study was a retrospective cohort study with patients in national registries. Of patients with MS in each country, >90% in Denmark and >80% in Sweden are part of the national registries. The study was limited to adults aged 18 to 55 years with clinically isolated syndrome or relapsing-remitting MS.

The primary outcome was disability progression based on a sustained increase in Expanded Disability Status Scale (EDSS) score at 24 weeks after initiating a DMT. Time to EDSS scores 3 and 4 and annualized relapse rate were 2 of the secondary outcomes.

The cohorts were largely similar at baseline before taking any DMT. The follow-up time in the study was 4.4 years for the 2161 patients in the Danish cohort and 3.7 years for the 2700 patients in the Swedish cohort.

The investigators confirmed that the Danish strategy was escalation while the Swedish strategy was greater use of highly effective DMT as a first therapy. As a first-line treatment, a low to moderately effective DMT was used in 92.4% of patients in the Danish cohort compared with 65.5% of patients in the Swedish cohort. A second-line or moderately to highly effective DMT was prescribed as the first treatment in 7.6% of patients in the Danish cohort and 34.5% in the Swedish cohort. Furthermore, patients in the Swedish cohort were also more likely to use a highly effective DMT as a second choice of therapy after discontinuation of a low to moderately effective DMT than patients in the Danish cohort.

For the primary outcome, the investigators found that the Swedish strategy was associated with a 29% reduction in the rate of disability progression compared with the Danish strategy at 24 weeks after treatment initiation (P = .004). The Swedish strategy was also associated with a 24% reduction in the rate of reaching an EDSS score of 3 and a 25% reduction in the rate of reaching an EDSS score of 4 compared with the Danish strategy (P = .03 and P = .01, respectively).

Consistent with the reduced rate of disability progression in Sweden, the overall annualized relapse rate was 50% lower in the Swedish cohort compared with the Danish cohort (P <.001).

The results of the study suggested that differences in treatment strategy for relapsing-remitting MS at the national level were associated with statistically significant differences in disease progression. Moreover, “starting with a more effective therapy and switching to a more effective DMT at treatment discontinuation irrespective of reason seemed to be superior to commencing a conventional first-line DMT and escalation,” the investigators concluded.


Spelman T, Magyari M, Piehl F, et al. Treatment escalation vs immediate initiation of highly effective treatment for patients with relapsing-remitting multiple sclerosis: data from 2 different national strategies. JAMA Neurol. 2021;78:1197-1204.

Related Items

Subscribe to Value-Based Care in Neurology

Stay up to date with the latest news in neurology by subscribing to receive the free VBCN e‑Newsletter.