Relapsing-remitting multiple sclerosis (RRMS) patients in Sweden have lower rates of increased disability than those who live in Denmark, a neighboring country in Scandinavia. According to a new study, this is most likely due to treatment protocol differences in each country.

Researchers and clinicians had posed the question: when a patient with MS begins on a DMT, should treatment commence with a less effective albeit safer pharmaceutical, or would it be more advantageous to commence treatment with a high-efficacy pharmaceutical known to carry a greater risk of side effects?

The study, “Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients with Relapsing-Remitting Multiple Sclerosis,” was published in JAMA Neurology. (JAMA Neurol. 2021;78(10):1197-1204. doi:10.1001/jamaneurol.2021.2738) Note: Seven of the study’s 10 researchers have financial links to pharmaceutical companies that market DMTs.

Researchers conducting the study wrote: “This study shows that, for the first time to our knowledge, differences in national treatment recommendations and strategies had a significant association with disability outcomes after a few years of follow-up,”.

In Sweden and Denmark, the customary practice has been to start treatment with safer, lower-efficacy DMTs. In the last decade, however, treatment with high-efficacy DMTs as a first-line treatment has increased significantly in Sweden, but not so in Denmark. Researchers in Sweden and Denmark began to investigate the differences to assess whether the differing treatment strategies led to different clinical outcomes.

The team reported: “While both countries have similar socioeconomic standards and health care systems, the choice of DMT and the treatment strategy for RRMS demonstrate significant differences. The objective of this retrospective cohort study … was to investigate whether national treatment recommendations and clinical practice are associated with disability outcomes after 3 to 7 years of follow-up.”

Researchers identified data for people with RRMS who had started on a first-line DMT from 2013 to 2016 through national registries in each country. Altogether, the group identified 2,700 patients in the Swedish registry (mean age of 36.1 years) and 2,161 in the Danish registry (mean age of 37.3 years). About two-thirds of the patients were female in either group.

The vast majority of Danish patients (92.4%) were started on a low-to-moderate efficacy DMT, such as Aubagio (teriflunomide). By contrast, in the Swedish registry, 65.5% started on a low-to-moderate efficacy DMT, while 34.5% started on a high-efficacy DMT such as Ocrevus (rituximab), Tysabri (natalizumab), or Gilenya (fingolimod).

Analysis revealed that the rate of 24-week confirmed increased disability in patients was statistically significant being much lower, by approximately 29%, among patients on the Swedish treatment protocol compared to patients on the Danish protocol. Disability improvement rates were similar in the two countries.

On the expanded disability status scale (EDSS), the risk of progressing to a score of 3 or higher, which would represent moderate disability, was also greatly reduced, by approximately 24%, with the Swedish treatment protocol. The risk of progressing to substantial disability (EDSS score of 4 or higher) was reduced by about 25% with the Swedish protocol.

“Swedish patients had a significantly lower rate of disability progression than Danish patients during an observational time of 3 to 7 years, and fewer Swedish patients reached thresholds of clinically evident disability compared with Danish patients,” the researchers wrote. “Early intervention with a more effective DMT was more prevalent in the Swedish cohort and may have been the main factor associated with the better disability outcome that we observed among Swedish patients,” they added.

Patients in Sweden were about 12% less likely to switch to a different medication, and were 22% less likely to discontinue treatment altogether.

In Denmark, the most common reason for discontinuing treatment with the initial DMT, which was reported in 37.4% of patients, was absence of efficacy. A smaller proportion (30.7%) of patients in Sweden discontinued treatment due to absence of efficacy.  However, the most common reason for treatment discontinuation was side effects (34.5%). According to the researchers, these differences likely reflect the different treatment protocols used in each country. Based on the results, the team concluded “that escalation of treatment was inferior to using a more effective disease-modifying treatment as initial treatment for multiple sclerosis.”

© 2022 Guiomar Goransson