Danish researchers discovered that the use of more efficacious disease-modifying therapy (DMT) as an initial treatment strategy for patients with relapsing-remitting multiple sclerosis (RRMS) provided better patient outcomes compared to treatment escalation, according to a study published in JAMA Neurology. 

Over the years, different branches of thinking have emerged regarding the best treatment strategy for patients with RRMS. This has caused a divergence in national guidelines on treatment protocols for RRMS patients. One line of thinking proposes that a first-line agent should initially be used and escalated to a second-line agent once signs of breakthrough disease activity are observed; this is known as the “treatment escalation” strategy. 

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Another line of thinking proposes that a highly effective DMT be used from the onset when high disease activity is observed; this is known as the “highly effective DMT” strategy. Both strategies have evidence that supports their efficacies. Researchers decided to compare the national treatment recommendations between 2 countries, Denmark and Sweden, and they found 2 major differences.

The first difference is in the use of the teriflunomide, a low to moderately effective DMT. Danish guidelines recommend the first-line use of teriflunomide in patients with RRMS in whom mild to moderate disease activity is observed. Swedish guidelines initially dictated that teriflunomide should only be used if another DMT, interferon-beta, failed; however, teriflunomide later received a full indication in 2016.

The second difference between the 2 countries is that rituximab, a powerful off-label DMT, has been increasingly used in Sweden, initially as a second- and third-line therapy; however, its use as a first-line therapy has become much more common. 

Sweden and Denmark are comparable in terms of socioeconomic status and healthcare standards, thus researchers set out to determine if the different national guidelines on treating RRMS resulted in differences in disability outcomes 3 to 7 years after follow-up.

In the Danish cohort: 

  • 2161 patients from the Danish registry who were started on a DMT between 2013 and 2016 were recruited.
  • 1996 (92.4%) patients were started on a low to moderately effective DMT.
  • 165 (7.6%) patients were started on a highly effective DMT.

In the Swedish cohort: 

  • 2700 patients from the Swedish registry who were started on a DMT between 2013 and 2016 were recruited.
  • 1769 (65.5%) patients were started on a low to moderately effective DMT.
  • 931 (34.5%) patients were started on a highly effective DMT.

The results showed that the Swedish RRMS treatment protocol produced better clinical outcomes than the Danish protocol. Compared to the Danish treatment protocol, the Swedish protocol was associated with: 

  • A 29% reduction in the rate of postbaseline 24-week confirmed disability worsening
  • A 24% reduction in the rate of RRMS patients reaching an Expanded Disability Status Scale (EDSS) of 3
  • A 25% reduction of in the rate of RRMS patients reaching an EDSS of 4.

This study elucidates how a slight difference in treatment protocol can achieve vastly different clinical outcomes. The authors of the study concluded, “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.” 

Reference

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