Not every Danish fairy tale has a happy ending

Introduction Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with extensive primary demyelination, inflammation, and progressive neurodegeneration
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Since the past ten years, the prevalence of MS has been increasing, and 2.
1 million people worldwide are affected by this every year
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In recent years, with the development of new drugs, MS patients have more treatment options
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But the question also arises.
Which treatment strategy the patient should choose (early high-efficiency treatment or ascending step treatment) has become a hot topic in the field of MS treatment
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The concept of early high-efficiency or early strengthening is to make full use of the "golden window period" of MS treatment and initiate effective disease modification therapy (DMT) drugs as soon as possible to delay disease progression and improve the quality of life of patients
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In order to further explore the clinical benefits of early and effective treatment strategies for MS patients, the editor compiled 3 real-world studies that confirmed the deterioration of disability from 24 weeks, the 5-year changes in the Extended Disability Status Scale (EDSS) score, and continued disability accumulation.
(SAD) time and the proportion of patients with no evidence of disease activity (NEDA) in the first year and the second year after the initial use of high-efficiency DMT drugs were analyzed and compared.
First-order treatment may be more beneficial for patients with MS
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Next, follow the editor and walk into the real world of MS.
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Compared with upgrading treatment, DMT seems to be more effective in early and effective treatment of RRMS patients.
1 This real-world study included 4861 cases (Denmark, n=2161, and more First-order treatment strategy is the main; Sweden, n=2700, the proportion of early use of high-efficiency drugs is higher than that of Denmark) 18-55-year-old clinically isolated syndrome (CIS) or RRMS adult patients, analysis indicators include RRMS patients confirmed at 24 weeks Disability worsening, 24 weeks confirmed disability improvement, time to reach EDSS scores of 3 and 4, drug withdrawal rate, annual recurrence rate, etc.
, aiming to analyze two different developed countries, Denmark and Sweden, using different DMT strategies ( The effect of early high-efficiency vs.
upgrade treatment) on the clinical outcome of patients with relapsing-remitting multiple sclerosis (RRMS)
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The results showed that compared with upgrading treatment, the incidence of disability worsening confirmed in 24 weeks in the early high-efficiency strategy group was significantly reduced by 29%; the proportion of EDSS scores 3 and 4 was significantly reduced by 24% and 25%, respectively; drug withdrawal rate and recurrence The rates are significantly lower
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The study showed that at the national level, there is a significant correlation between differences in RRMS treatment strategies (early high-efficiency vs.
upgrade treatment) and disability outcomes
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Early and high-efficiency treatment of DMT has obvious clinical benefits, and it seems to be more effective than upgrade treatment
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So, is there still a difference in long-term clinical outcomes between early high-efficiency treatment and upgrade treatment? Early and efficient treatment of initial DMT with better long-term clinical outcomes.
2 This real-world study included data on 720 patients (592 remaining after exclusion) of MS patients treated with DMT
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According to the first treatment strategy, it is divided into high-efficiency DMT group (early high-efficiency treatment, EIT) and intermediate-effective DMT group (upgrade treatment, ESC)
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The primary study endpoint is the 5-year change in the EDSS score, and the secondary study endpoint is the SAD time.
It aims to analyze the long-term results of a population-based cohort under different initial DMT treatment strategies (early high-efficiency vs.
upgraded treatment)
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The results showed that the 5-year change in the EDSS score of the EIT group was significantly lower than that of the ESC group (0.
3 vs.
1.
2), and after adjusting for the relevant covariates, the change was still significant (Table 1); Table 1 The initial DMT strategy and the 5-year Correlation of changes in EDSS score: adjusted linear regression modela Abbreviation: DMT, disease modification treatment; EDSS, extended disability status scale; EIT, early intensive treatment aInitial DMT strategy includes: early enhancement/early high efficiency (n=41 ) vs upgrade treatment (n=138) Compared with the ESC group, the median time to SAD in the EIT group was significantly delayed (6.
0 vs.
3.
14 years, p=0.
05); in the ESC group, patients who were upgraded to high-efficiency DMT treatment The median time to SAD was 3.
3 years (95% CI, 1.
8-5.
6; log-rank test p=0.
08 compared with EIT group), and 60% of patients in this group achieved SAD during the initial intermediate treatment before upgrade
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For patients who continue to use moderately effective DMT, the median time to SAD is 3.
1 years (95% CI, 2.
6-4.
0; log-rank test p=0.
07 compared with EIT group)
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The study showed that, in the real world, early and high-efficiency DMT strategies have better long-term outcomes for patients than upgraded treatment strategies-the 5-year change in EDSS scores is significantly reduced, and the median time to SAD is significantly delayed
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Through the above real-world studies, it can be seen that MS patients who use early and high-efficiency treatment can benefit in terms of improving disability progression, and have better long-term clinical outcomes compared with upgraded treatment
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In the first few years of diagnosis of patients, limited disease activity is widely regarded as a sign of good prognosis
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So, what is the impact of early effective treatment on patients reaching NEDA-3 status? Early and effective treatment of initial DMT is more likely to reach NEDA-3.
3 This study included 3951 cases of MS patients from southeastern Norway who received intermediate-effective DMT and/or high-efficiency DMT for at least 12 months (excluded conditions are detailed See the original text), which aims to analyze the real-world research based on the Norwegian population.
Different initial treatment options (moderate-effective DMT vs.
high-efficiency DMT) for MS patients achieve NEDA-3 in the next 1 and 2 years (proposed in 2014 , Because it contains three composite indicators: ARR, MRI active lesions and EDSS score, it is named "NEDA-3")
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The results showed that compared with patients who started using intermediate-acting DMT as the first treatment drug, patients who started using high-efficiency DMT as the first treatment drug had a higher proportion of NEDA-3 in the first and second years (the first 1 year, 68.
0% vs.
36.
0%; in the second year, 52.
4% vs.
19.
4%) (Table 2); Table 2 Under different treatment strategies, patients reaching NEDA in the first and second years are highly effective in the first year Compared with patients who used intermediate-acting DMT drugs as the first treatment drug, the odds ratio (OR) value of NEDA-3 reached 3.
9 (95% CI, 2.
4-6.
1, p<0.
001).
The OR value in the second year was 4.
6 (96%CI, 2.
8-7.
6, p<0.
001) (Table 3); Table 3 was used to analyze the OR value of NEDA in the first and second years under different treatment strategies through binary logic.
Note : Stratified by risk and adjusted according to the age of starting the medication, the time from the onset to the beginning of the medication, and gender.
This study shows that the initial high-efficiency DMT drug is compared with the initial intermediate-effective DMT drug, and the patients will be in the next 1 and 2 years The possibility of reaching NEDA-3 is significantly higher, and the prognosis is better; and the preferred treatment plan is the most important.
In the clinical diagnosis and treatment process, for MS patients, high-efficiency DMT drugs should be used as the first treatment option and initiated as soon as possible To grasp the "window period" of treatment; at the same time, the author suggests that the immunomodulatory treatment guidelines should be updated to ensure early and efficient planned treatment for most patients diagnosed with MS
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Expert comment on expert profile Professor Hu Xueqiang, the leader of the Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University, the second-level professor, the first-level chief physician, and the doctoral supervisor.
Editor-in-chief of the Journal of He Neurology Legal representative and vice president of the Guangdong Stroke Association Former Deputy Chairman of the Neurology Branch of the Chinese Medical Association Former Leader of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association Former Deputy Editor-in-Chief of the Chinese Journal of Neurology Former Chairman of the Neurology Branch of the Guangdong Medical Association, Former Director of the Department of Neurology and Department of the Third Affiliated Hospital of Sun Yat-sen University Expert" title
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Won one third prize of Guangdong Provincial Science and Technology Achievement Award; two third prize of Provincial Natural Science Award; one second prize of Guangdong Science and Technology Achievement Award; two second prize of Science and Technology Progress Award of the State Education Commission; one second prize of Science and Technology Progress Award of the Ministry of Education
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One first prize for excellent papers from the Ministry of Health and Chinese Medical Association, and the second prize for the fifth "Wu Jieping Medical Research Award, Paul Janssen Pharmaceutical Research Award"
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Over the past 40 years, he has been engaged in neurological medical care, teaching, and scientific research
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In scientific research, he is mainly engaged in the research of neuroimmune diseases, cerebrovascular diseases, and neurogenetic diseases.
More than 300 papers have been published (the corresponding author has published more than 80 SCI papers), and the editor-in-chief published "Multiple Sclerosis" (People's Medical Publishing House) , "Prevention and treatment of primary cardiovascular and cerebrovascular diseases" (China Military Medical Press), "New Advances in Neuroimmune Diseases" (Sun Yat-sen University Press), popular medical science "Stroke" (Sun Yat-sen University Press) and other books
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In the early stage of MS patients, RRMS is the mainstay.
If timely and effective DMT treatment is not available, as the age increases and the disease progresses, the remyelination and repair effects are weakened, and the patient will be converted to SPMS more quickly, and irreversible neurodegeneration will occur.
Sexual disease, aggravated disability, and decreased cognitive function
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In the 1990s, the successful listing of IFNβ-1b and Glimet Acetate changed people’s attitudes towards MS treatment, making the treatment of MS focus not only on symptomatic treatment, but also on “disease modification treatment”; in 2010, the first Fingolimod, an oral DMT drug, was approved for marketing, ushering in a new era of oral treatment for MS
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At the ECTRIMS conference held recently, Professor Xavier Montalban introduced some guidelines in the ECTRIMS/EAN multiple sclerosis drug treatment guidelines updated in 2021.
Among them, for the "early treatment decision", Professor Xavier Montalban emphasized that "it should be based on Disease activity (whether clinical or MRI activity) and patient characteristics, consider choosing a disease-modifying drug (DMD) with higher efficacy at an early stage
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"The recommendations in the guidelines will be a milestone in the management of MS disease in the next few years
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The above real-world studies have shown that early and effective DMT drug therapy has significant benefits in terms of disability progression, clinical outcomes, and the possibility of reaching NEDA-3 compared with advanced treatment
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In addition, the international community has increasingly recognized the strategy of early initiation of high-efficiency DMT drug therapy
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In the management of the whole course of MS patients, early and standardized management is very important.
It is necessary to seize the "window period" of early treatment of the disease.
According to the individual condition of the patient, select high-efficiency DMT drugs for treatment as soon as possible to control inflammation and prevent occurrence Progress, realize more benefits and improve the quality of life
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At present, the domestically marketed sphingosine 1-phosphate (S1P) receptor modulators-fingolimod and sinimod, are highly effective oral DMT drugs approved by most doctors, which can more accurately regulate lymphocytes.
Leave it in the lymph nodes to reduce peripheral inflammation
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Among them, the molecular structure optimized by Sinimod is easier to cross the blood-brain barrier, control inflammation in the central nervous system, promote remyelination, and realize nerve repair.
It has made a big step forward from the mechanism and has been better filled for many years.
The gap in the field of MS treatment since then is worthy of our vigorous promotion in the clinic
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We believe and expect that in the future, Sinimod can benefit more MS patients and bring hope to more families! References: 1.
Tim Spelman, et, al.
JAMA Neurology.
2021 August 16:E1-E8.
2.
KH,et,al.
JAMA Neurology.
2019;76(5):536-541.
doi:10.
1001/jamaneurol .
2018.
4905.
3.
Cecilia Smith Simonsen,et,al.
Front.
Neurol.
doi: 10.
3389/fneur.
2021.
693017.