Highly effective disease-modifying treatment superior to escalation in relapsing-remitting MS

According to study results, the use of highly effective disease-modifying treatment (DMT) in patients with relapsing-remitting multiple sclerosis (RRMS) in Swedish patients is associated with lower CDW and relapse rates than Danish patients published in JAMA Neurology.

In MS, DMTs are used to slow the progression of the disease and can vary depending on the doctor’s and patient’s treatment strategy. The DMTs may be highly effective with a higher risk of side effects, or they may be less effective with a better safety profile. This becomes a mystery to clinicians as they initiate treatment for MS.

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

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In the primary analysis, the researchers compared the time to 24 weeks of confirmed disability worsening (CDW), defined as an increase in EDSS (Expanded Disability Status Scale) score of at least 1 point from baseline that occurred between 2 follow-up exams none were sustained less than 6 months apart. A total of 1.5 points was awarded if the baseline EDSS score was 0 and 0.5 points if the EDSS baseline score was 5.5 or greater. Secondary endpoints included a 24-week confirmed improvement in disability, milestone EDSS scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switch.

Eligible were adult patients aged 18 to 55 years with clinically isolated syndrome or RRMS who had initiated DMT for the first time between January 2013 and December 2016. The cohort comprised 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 weak to moderately effective DMT as their first treatment, with teriflunomide being the most common first-line treatment (42.0%). Of the Swedish participants, 1769 (65.5%) started therapy with a weak to moderately effective DMT, with dimethyl fumarate (22.8%) and interferon beta-1a (22.8%) being the most frequently used DMT of first choice .

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

The total mean follow-up was 4.1 ± 1.5 years – 4.4 ± 1.5 years for the Danish patients versus 3.7 ± 1.4 years for the Swedish participants. The Swedish treatment strategy was associated with a 29% reduction in the rate of 24-week CDW compared to the Danish treatment strategy (inverse probability of treatment-weighted hazard ratio) [HR], 0.71; 95% CI, 0.57-0.90; P = 0.004).

The Swedish vs. Danish treatment strategy was with a 24% reduced rate of achieving an EDSS score of 3 (HR 0.76; 95% CI 0.60-0.97; P = 0.03) and a 25% rate A reduction in the achievement rate was associated with an EDSS score of 4 (HR 0.75; 95% CI 0.61-0.96; P = 0.01).

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

“Starting with more effective therapy and switching to a more effective DMT upon discontinuation, regardless of the reason, appeared to be superior to starting conventional first-line DMT and escalating,” commented the researchers.

Disclosure: Some of the study authors stated links with pharmaceutical companies. For a full list of specifications, see the original reference.


T. Spelman, M. Magyari, F. Piehl 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

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