High-Efficacy Disease-Modifying Treatment Superior to Escalation in Relapsing-Remitting MS

Relapsing-remitting Multiple sclerosis diagnosis in form.
Researchers compared the effect of high-efficacy DMTs and treatment escalation with regard to the reduction of confirmed disability worsening rates in relapsing-remitting multiple sclerosis.

Use of highly effective disease-modifying treatment (DMT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a lower rate of confirmed disability worsening (CDW) and relapse outcomes in Swedish patients compared with Danish patients, according to study results published in JAMA Neurology.

In MS, DMTs are used to slow disease progression and can vary depending on clinician and patient treatment strategy. The DMTs can be highly effectively with a greater risk for side effects, or they can be less effective with a better safety profile. This becomes a conundrum for clinicians when initiating MS treatment.

In the current study, the researchers retrospectively analyzed data from Swedish and Danish nationwide MS registries to determine whether national treatment recommendations and clinical practice are associated with disability outcomes after 3 to 7 years.

In the primary analysis, the researchers compared time to 24-week confirmed disability worsening (CDW), defined as an increase in Expanded Disability Status Scale (EDSS) score with at least 1 point from baseline sustained between 2 follow-up visits that were no less than 6 months apart. A total of 1.5 points were given if the EDSS score at baseline was 0, and 0.5 points were given if the baseline EDSS score was 5.5 or more. Secondary outcomes included 24-week confirmed disability improvement, milestone EDSS scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching.

Eligible participants were adult patients aged from18 to 55 years with clinically isolated syndrome or RRMS who initiated DMT for the first time between January 2013, and December 2016. The cohort included 2700 patients from the Swedish registry (69.2% women; mean age, 36.1±9.5 years) and 2161 patients from the Danish MS registry (68.1% women; mean age, 37.3±9.4 years).

A total of 1966 Danish patients (92.4%) began therapy with a low to moderately effective DMT as their first treatment, with teriflunomide as the most common first-line treatment (42.0%). Among Swedish participants, 1769 (65.5%) began therapy with a low to moderately effective DMT, with dimethyl fumarate (22.8%) and interferon beta-1a (22.8%) as the most frequently used first-line DMT.

A total of 931 Swedish patients (34.5%) compared with 165 Danish patients (7.6%) initiated first-line treatment with a second-line or moderately to highly effective DMT, such as rituximab, natalizumab, or fingolimod.

The overall mean follow-up was 4.1±1.5 years — 4.4±1.5 years for the Danish patients vs 3.7±1.4 years for the Swedish participants. The Swedish treatment strategy was associated with a 29% reduced rate of 24-week CDW compared with the Danish treatment strategy (inverse probability of treatment weighting hazard ratio [HR], 0.71; 95% CI, 0.57-0.90; P =.004).

The Swedish vs Danish treatment strategy was associated with a 24% reduced rate of achieving an EDSS score of 3 (HR, 0.76; 95% CI, 0.60-0.97; P =.03), and a 25% decrease in the rate of achieving an EDSS score of 4 (HR, 0.75; 95% CI, 0.61-0.96; P =.01).

Study limitations included the retrospective and observational nature of the data. In addition, the researchers used 24-week confirmed disability progression as the primary outcome while they used 24-week disability improvement, time to achieve an EDSS score of 3 and 4, annualized relapse rate, and time to first relapse as secondary outcomes. Disability progression is the essential outcome in MS and may be more reliable than relapse rate in evaluating MS treatment.

“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 researchers commented.

Disclosure: Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.


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. Published online August 16, 2021. doi:10.1001/jamaneurol.2021.2738