In the same two developed countries, different choices brought about completely different endings!

Multiple sclerosis (MS) is currently one of the most common disabling neurological diseases in young adults in the world1
.

In the 1990s, IFNβ-1b and Glimer Acetate were launched, and MS disease modification treatment (DMT) was started; in 2010, the first oral DMTs drug fingolimod was launched, which opened a new era of oral MS treatment! In the past, due to the lack of DMTs, for MS patients in remission, the upgrade treatment strategy was generally adopted; in recent years, with the development of clinical research on new drugs, more and more treatment options have been brought to MS patients
.

The treatment strategy of DMTs has always been a hot topic in the field of MS treatment.
More and more experts and scholars have begun to pay attention to early and efficient (also known as "inverted pyramid" therapy) treatment strategies; 2018 AAN Guide 2 recommends that MS patients should be as early as possible Carry out DMT intervention and grasp the golden treatment window for MS
.

However, there are relatively few real-world studies on early effective treatment strategies.
Recently, a report published in JAMA Neurology entitled "Comparison of treatment strategies from 2 different countries: Relapsing-remitting multiple sclerosis (RRMS) patients The real-world study of "Upgrading Treatment vs.
Early Efficient Treatment" has better confirmed that early and efficient treatment strategies are better! Upgrading treatment strategy: Start with low/medium-acting DMT drugs, and when there are signs of breakthrough progress in disease activity, switch to DMT drugs that are considered more effective
.

Early high-efficiency strategy: start high-efficiency DMT drugs as soon as possible and grasp the golden treatment window period
.

A total of 4861 RRMS patients were included in the study.
Different DMTs treatment strategies (upgrading treatment vs.
early high-efficiency treatment) were used in Denmark and Sweden.
The patient’s disability worsening confirmed at 24 weeks and reaching the Extended Disability Status Scale (EDSS) were compared and analyzed.
) The difference between 3 points and 4 points, drug withdrawal rate, treatment conversion rate, annual recurrence rate and other indicators
.

The results show that there is a significant correlation between the difference in RRMS treatment strategies and the patient's disability outcome
.

The early high-efficiency treatment strategy of DMTs is more effective than upgrading treatment, and has obvious clinical benefits
.

Research overview 1.
Research methods This study included adult patients with clinical isolated syndrome (CIS) or RRMS aged 18-55 who were treated with DMT for the first time between January 1, 2013 and December 31, 2016 (excluding baseline time Patients with progressive MS or secondary progressive MS and patients older than 55 years old)
.

The data from the patient's first DMT treatment to the last follow-up (October 2, 2019) were selected for analysis
.

The treatment strategy of RRMS differs significantly between Sweden and Denmark: Denmark (upgrading treatment strategy): 2161 MS patients registered from the Danish Medical Registry: 1994 (92.
3%) initially used low/medium effective DMT drugs ( Teriflunomide 42.
0%), and another 165 (7.
6%) started using high-efficiency DMT drugs (rituximab 0.
1%, natalizumab 4.
8%, fingolimod 2.
7%)
.

Sweden (early high-efficiency strategy): 2700 MS patients registered from the Swedish Medical Registry: 1769 (65.
5%) initially used a low/medium effective DMT drug (teriflunomide 2.
4%), and another 931 (34.
5) %) Use high-efficiency DMT drugs (rituximab 17.
9%, natalizumab 11.
1%, fingolimod 5.
5%) at the beginning (Table 1)
.

Table 1 Comparison of baseline characteristics of different cohorts 2.
Main endpoint of evaluation indicators: Disability deterioration confirmed at 24 weeks; Secondary endpoint: Disability improvement confirmed at 24 weeks, time to reach Extended Disability Status Scale (EDSS) scores of 3 and 4, Annual recurrence rate, time to first recurrence, and treatment conversion
.

3.
The results of the study Compared with the Danish treatment strategy (upgrading treatment), the Swedish treatment strategy (early and efficient): 1.
The incidence of disability worsening confirmed at 24 weeks after baseline was significantly reduced by 29% (HR, 0.
71; 95% CI, 0.
57-0.
90; p=0.
004) (Figure 1); Figure 1 Cohort with different treatment strategies 24 weeks to confirm disability progression time 2.
The proportion of reaching 3 and 4 points on the Extended Disability Status Scale (EDSS) was significantly reduced by 24% (HR , 0.
76; 95%CI, 0.
60-0.
97; p=0.
03)\25% (HR, 0.
75; 95%CI, 0.
61-0.
96; p=0.
01)
.

During the follow-up period: the mean (SD) time to reach an EDSS score of 3 for the Danish cohort was 1.
7 (1.
2) years, while the Swedish cohort was 2.
2 (1.
5) years
.

The mean (SD) time for the Danish cohort to reach EDSS score 4 was 2.
6 (1.
6) years, while the Swedish cohort was 3.
9 (1.
4) years
.

3.
The discontinuation rate was significantly reduced by 22% (HR, 0.
78; 95% CI, 0.
71-0.
68; p<0.
001); in the Danish cohort, lack of effectiveness was the most common reason for discontinuation of treatment (563 out of 1504 patients) Treatment was discontinued [37.
4%]), followed by adverse reactions (508 of 1504 patients discontinued treatment [33.
8%])
.

In the Swedish cohort, adverse reactions were the most common reason for discontinuation of treatment (587 of 1702 patients discontinued treatment [34.
5%])
.

The frequency of discontinuation of treatment due to lack of effectiveness is low (523 out of 1702 patients discontinued treatment [30.
7%])
.

4.
The treatment conversion rate was significantly reduced by 12% (HR, 0.
88; 95% CI, 0.
78-0.
98; p=0.
02); in the Danish cohort, 1994 (92.
3%) patients who started using moderate/low effective DMT drugs , 554 patients (27.
8%) switched to high-efficiency DMT; out of 1504 patients who discontinued the drug, 534 patients (35.
5%) switched to other DMT.
Fingolimod was the most common choice (of 1504 patients who discontinued the drug 290 cases [19.
3%])
.

In the Swedish cohort, of 1685 (62.
4%) patients who started using moderate/low-efficiency DMT drugs, 585 (34.
7%) switched to high-efficiency DMT; out of 1702 patients who discontinued the drug, 859 patients (50.
5%) Switch to other DMT
.

5.
The annual recurrence rate of patients is lower (Denmark 0.
190 vs.
Sweden 0.
078, p<0.
001) (Table 2, Figure 2)
.

Table 2: Annual recurrence rates of different cohorts Figure 2 Time to first recurrence of cohorts with different treatment strategies 4.
Research conclusions The results of this study show that at the national level, the difference in RRMS treatment strategies (early high-efficiency vs.
upgrade treatment) and disability There is a significant correlation between the outcomes
.

Early and high-efficiency treatment of DMTs is more effective than upgrading treatment, and has obvious clinical benefits
.

Summary DMTs are currently the standard treatment drugs for MS in remission recommended by domestic and foreign guidelines
.

In recent years, with the continuous advent of new drugs, the treatment goals of MS have been iteratively upgraded, and the treatment concepts have been constantly updated
.

A number of real-world studies 4.
5 confirmed that early high-efficiency DMTs treatment compared with upgrade treatment can significantly reduce the risk of secondary progressive MS (SPMS) and the cumulative risk of disability progression, and the changes in EDSS will also be significantly improved after 5 years
.

The results of this study also show that for patients with RRMS, early and high-efficiency treatment of DMTs is more effective than upgrading treatment.
The two confirmed disability worsening at 24 weeks, reaching the Extended Disability Status Scale (EDSS) 3 points and 4 points, and stopping There are significant differences in indicators such as drug rate, treatment conversion rate, and annual recurrence rate.
It can be seen that early and high-efficiency DMTs treatment can bring more benefits to patients, help more patients delay the progression of disability, and help more families to recover.
Tree confidence! Among the DMT drugs currently on the market in China, both sinimod and fingolimod belong to high-efficiency DMTs
.

Among them, Sinimod, as a national first-class innovative drug in the field of rare disease treatment in China, is currently the world’s first and only oral DMTs6 that has large clinical data to prove effective for patients with progressive relapsed MS (RMS).
Approved for the treatment of adult relapsing multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease
.

Fingolimod is currently the only DMT drug approved for the treatment of children 7.
8
.

Looking ahead, this research has certain limitations
.

Among the enrolled patients, the proportion of patients in the Swedish cohort who initially adopted the early and efficient strategy was higher (34.
5% in Sweden vs.
Denmark 7.
6%), and the proportion of patients in the Danish cohort who initially adopted the upgraded treatment strategy was higher (92.
3% in Denmark vs.
Sweden) 65.
5%), the study concluded that early high-efficiency is better than upgrading treatment
.

We are looking forward to the release of more high-quality and authoritative DMTs guidelines/consensus, and constantly updating the latest treatment concepts.
We hope that we can take advantage of the current rare disease policy in China to obtain better treatment outcomes for more patients.
.
.
.
.
.
The MCC number MAY2110409 is valid for 2022-10-12, and the data is expired and deemed invalid
.

  References: 1.
Neuroimmunology Branch of Chinese Society of Immunology, etc.
Chinese Journal of Neuroimmunology and Neurology.
2018,25(6):387-394.
2.
Rae-Grant A ,et,al.
Neurology.
2018 Apr 24;90 (17):777-788.
3.
Giovannoni G.
Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm[J].
Current opinion in neurology, 2018, 31(3): 233-243.
4.
Brown JWL, et al.
JAMA, 2019, 321(2): 175-187.
5.
Harding K, et al.
JAMA neurology, 2019, 76(5): 536-541.
6.
Kappos L,et,al.
Lancet.
2018 Mar 31;391( 10127):1263-1273.
7.
https:// 8.
Zeydan B, et al.
CurrNeurol Neurosci Rep .
2020 May 26;20(7)24.