JAMA Neurology: Relapsing-remitting multiple sclerosis, which treatment strategy is better?

In recent years, the clinical development of new disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RRMS) has resulted in more and more treatment options
.

The possibility of achieving personalized treatment decisions has also increased, and there are more and more guidelines and treatment plans to support clinicians and patients in choosing DMT

The most commonly used treatment strategy is to use first-line drugs first, and then switch to second-line drugs that are considered more effective when there are signs of breakthrough disease activity.
This often comes at the expense of safety and higher costs
.

The purpose of this escalation strategy is to find the best effective treatment while taking as little risk as possible

However, in cases with clinical or neuroradiological signs of high disease activity, it is often recommended to use a more effective DMT to reduce the risk of nerve tissue damage.
This may happen if the time to suppress inflammation is delayed.

.

In addition to the effectiveness of DMT, there are some reasons for switching treatment, such as safety, adverse events, planned pregnancy, tolerability, compliance, and cost

There are several pieces of evidence supporting the early treatment of multiple sclerosis (MS), including trials, observational studies, and post-marketing studies that delay the conversion of clinically isolated syndromes to MS
.

However, although there is evidence that delayed initiation of DMTs is related to future clinical outcomes, investigations of doctors' treatment practices have shown that DMTs are usually not initiated during clinically isolated syndromes (after the onset of symptoms but before the diagnosis of MS)

Three trials have shown that the effects of interferon β and glatiramer acetate are similar, but there is no RCT that is more efficient in a head-to-head manner.

Crelizumab, rituximab, or clarithromycin

manage

However, recent real-world evidence suggests that initiating high-efficiency treatment within 2 years after onset can improve the outcome of long-term disability compared to delayed initiation of treatment, indicating that the timing of switching treatment is important
.

Compared with delayed initiation of treatment, effective treatment within 2 years of onset can improve the outcome of long-term disability, indicating that the timing of switching treatment is important
.

Denmark and Sweden have established national multiple sclerosis registration data, covering more than 90% and 80% of patients, respectively
.

From September 2013 to 2019, teriflunomide became the first-line treatment recommended in Denmark for RRMS patients with mild to moderate disease activity, except for women with recent pregnancy plans

In Sweden, teriflunomide therapy was initially only approved for RRMS patients who failed interferon beta therapy.

It was not until 2016 that the full indications for RRMS were obtained

Another major difference in choosing DMT is that Sweden is increasingly using rituximab as an off-label treatment for MS
.
It has become the most frequently used DMT, initially as a second-line or third-line treatment, but in recent years, it has been increasingly used as a first-line option
.

Therefore, although these two countries have similar socio-economic standards and health care systems, the DMT selection and treatment strategies for RRMS show significant differences
.
This retrospective cohort study is based on data obtained from Swedish and Danish MS registries, and the purpose is to investigate whether national treatment recommendations and clinical practice are related to disability outcomes after 3-7 years of follow-up
.

They used data from 4861 patients in the National Multiple Sclerosis (MS) Registry of Denmark and Sweden, from the date of indexing DMT (between January 1, 2013 and December 31, 2016) to the time of data extraction The last recorded visit (October 2, 2019)
.

The main result of the study is the 24 weeks to confirm the deterioration of disability
.
The secondary outcome was 24 weeks of confirmed disability improvement , the landmark Expanded Disability Status Scale scores of 3 and 4, annualized recurrence rate, time to first recurrence, and treatment switch
.
Analyze the data using inverse probability of treatment weighting-based models, use propensity scores to weight, and compare the imbalances of confounding factors observed at baseline between the two countries
.

The main result of the study is the 24 weeks to confirm the deterioration of disability
.
The secondary outcome is the 24 weeks confirmed disability improvement

The Swedish Multiple Sclerosis Registry has a total of 2700 patients (1867 women [69.
2%]; mean [SD] age, 36.
1 [9.
5] years), and the Danish Multiple Sclerosis Registry has a total of 2161 patients (1472 women [68.
1 %]; average [SD] age, 37.
3 [9.
4] years) who started receiving the first DMT treatment from 2013 to 2016 and were included in the analysis.
The average observation time (SD) was 4.
1 (1.
5) years
.

A total of 1994 Danish patients (92.
3%) started using low-to-moderately effective DMT (Teriflunomide, 907 [42.
0%]), 165 (7.
6%) started using high-efficiency DMT, and a total of 1769 Swedish patients (65.
5 %) started to use low-to-moderately effective DMT (teriflunomide, 64[2.
4%]), and 931 (34.
5%) started to use high-efficiency DMT
.

Compared with the Danish treatment strategy, the Swedish treatment strategy was associated with a 29% reduction in the rate of disability deterioration confirmed 24 weeks after baseline (hazard ratio, 0.
71; 95% CI, 0.
57-0.
90; P = .
004)
.

Compared with Danish patients, the Swedish treatment strategy also reduced the rate of reaching 3 points on the expanded disability status scale by 24% (hazard ratio, 0.
76; 95% CI, 0.
60-0.
97; P = .
03) and reaching the expanded disability status The rate of 4 points on the scale decreased by 25% (hazard ratio, 0.
75; 95% CI, 0.
61-0.
96; P = .
01)
.

The results of the study indicate that there is a correlation between differences in RRMS treatment strategies and disability outcomes at the national level
.
The efficacy upgrade is not as good as the use of DMT with better efficacy as the initial treatment method
.

At the national level, there is a correlation between differences in RRMS treatment strategies and disability outcomes
.
The efficacy upgrade is not as good as the use of DMT with better efficacy as the initial treatment method
.

Original Source:
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 .
Published .
JAMA Neurol.
online August 16, 2021.
doi:10.
1001/jamaneurol.
2021.
2738

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.
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