Professor Jin Tao: A new treatment option for multiple sclerosis under the new pattern NCN2021

Hosted by the Chinese Medical Association and the Neurology Branch of the Chinese Medical Association, undertaken by the Guangdong Medical Association, and co-organized by the First Affiliated Hospital of Sun Yat-sen University and Zhuhai People’s Hospital of Guangdong Province, the 24th National Neurology Conference of the Chinese Medical Association is in full swing.
In progress
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On September 24, the multiple sclerosis academic session hosted by Bojian Company was widely praised by the participating experts
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This academic session sincerely invites Professor Guan Yangtai from Renji Hospital, Shanghai Jiaotong University School of Medicine, as the chair Select the wonderful report
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This article will briefly summarize the wonderful content for readers
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Expert Profile Professor Guan Yangtai • Director, Chief Physician/Professor, and Doctoral Supervisor of the Department of Neurology, Renji Hospital Affiliated to Shanghai Jiaotong University School of MedicineProfessor Jin Tao • Deputy Director, Chief Physician, Professor, PhD Supervisor, Department of Neurology, Bethune First Hospital, Jilin University There are many challenges in the treatment of multiple sclerosis (MS) 1.
MS is currently one of the most common disabling neurological diseases in young adults in the world.
In 2016, the number of MS patients worldwide was about 2.
22 million, with a prevalence rate of 30.
1 per 100,000, since 1990 The annual growth rate was 10.
4%; the number of MS patients in Mainland China exceeded 100,000, an increase of 45.
6% since 1990
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After adjusting for age and gender, the incidence of MS in China is 0.
235/100,000/year; the geographic distribution of MS is related to the north-south latitude gradient and the east-west altitude gradient.
Residents in high latitudes and high altitude areas are more likely to develop MS; females are more likely to develop MS.
The rate is about 2.
02 times that of men, and the peak age of onset is 40-49 years old (Figure 1)
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Figure 1 The crude incidence of MS in men/women of all ages from 2016 to 2018 2.
The high disability of MS leads to a decline in the social labor force and an increase in social burden.
Studies have shown that as disability progresses, MS patients (<retirement age) participate The proportion of jobs dropped from 82% (EDSS=0) to 8% (EDSS=9)
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Data from the 2020 Comprehensive Social Survey of Patients with Multiple Sclerosis in China shows that as many as 88.
5% of the respondents are unemployed and out of school due to multiple sclerosis; more than 43% of patients cannot take care of themselves completely and need care by others
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3.
The pathology and symptoms of MS are heterogeneous, which increases the difficulty of long-term management of the disease.
MS is a complex and progressive central nervous system demyelinating disease.
Its etiology may be related to immunity, susceptibility genes, infection, and environment.
And other factors are related (Figure 2)
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MS is pathologically manifested by multiple features of central nervous system (CNS) such as multiple demyelination, inflammation, and axon degeneration
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MS clinical manifestation, its common symptoms include decreased vision, double vision, limb sensory disturbance, limb movement disorder, ataxia, bladder or bowel dysfunction and so on
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At all stages of MS, active patient-centered management is advocated to minimize the impact of the disease, maximize the quality of life, and cultivate the concept of health.
Dealing with the symptoms of MS is a key component of disease management
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Figure 2 MS pathology and symptoms are heterogeneous.
Dimethyl fumarate enteric-coated capsules are a new option for disease modification therapy (DMT).
MS is a lifelong disease, and the main goal of remission treatment is to control disease progression
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The remission period is the ideal time window for MS treatment (Figure 3).
From CIS to RRMS, the chance of establishing an effective treatment gradually decreases
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Figure 3 MS disease progression and ideal time window for treatment.
Domestic and international guidelines/consensus recommends that DMT treatment should be initiated as soon as possible during MS remission (Figure 4).
According to the analysis of the survival report data of Chinese multiple sclerosis patients in 2021, the current DMT treatment rate in China is only It is 18%, which is far lower than the treatment rate (80%) in the United States and the European Union
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Figure 4 Domestic and international guidelines/consensus recommends that DMT treatment should be initiated as soon as possible during MS remission.
However, the availability of DMT drugs in China lags behind that in Europe and the United States (22 in total), and only 3 DMTs in China are included in the medical insurance list, dimethyl fumarate It was newly approved in 2021 and is currently preparing to enter medical insurance
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1.
Dimethyl fumarate is the world's most prescribed MS oral DMT drug.
More than 500,000 patients received treatment.
In April 2021, dimethyl fumarate enteric-coated capsules were approved in China for the treatment of adult RMS.
Including CIS, RRMS and active SPMS
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Dimethyl fumarate is the world's most prescribed oral DMT drug for multiple sclerosis.
More than 500,000 patients worldwide have witnessed the efficacy and safety of dimethyl fumarate, providing more treatment options for RMS patients
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2.
The dual mechanism of dimethyl fumarate: acting on the peripheral immune and central nervous system at the same time, coping with the pathogenesis of MS.
The existing DMT drugs in China mainly act on the peripheral immunity, and drugs with new mechanisms of action are needed to deal with MS heterogeneity Sex
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Dimethyl fumarate has a dual mechanism of central nervous system and immune regulation (Figure 5): In the central nervous system, dimethyl fumarate can affect neurons, oligodendrocytes, and small glial cells through a variety of pathways.
Plasma cells and astrocytes have a direct role in protecting the central nervous system
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At the same time, dimethyl fumarate regulates the peripheral immune system by regulating the number and function of different types of lymphocytes
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Numerous guidelines/consensus and authoritative journal reviews have listed dimethyl fumarate as the first-line DMT drug (Figure 6)
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Figure 5 The dual mechanism of dimethyl fumarate Figure 6 Guidelines/consensus and authoritative journal review recommendations 3.
After receiving dimethyl fumarate treatment for 10 years, 45% of RMS patients have no recurrence, and 77% of RMS patients cannot walk A comprehensive analysis of the restricted phase III study DEFINE and CONFIRM studies (Figure 7) showed that after 2 years of dimethyl fumarate treatment, the annual recurrence rate was reduced by 49%, and the risk of disability progression was reduced by 32%
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Figure 7 DEFINE and CONFIRM study results The ENDORSE study is an extended follow-up study of the DEFINE and CONFIRM study (Figure 8).
The follow-up was up to 13 years.
The study showed that after 10 years of treatment with dimethyl fumarate, 45% of patients had no recurrence.
77% of patients have unrestricted walking
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Figure 8 Results of the ENDORSE study.
In addition, Professor Jin Tao also introduced the Danish national cohort study and the Swiss cohort study
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Real-world studies have confirmed that dimethyl fumarate has a significantly better efficacy than teriflunomide in controlling recurrence, and the withdrawal rate due to disease progression is lower than that of teriflunomide
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In terms of controlling disease progression, dimethyl fumarate is as effective as fingolimod
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4.
The safety of dimethyl fumarate is controllable, and there is no need for additional initial monitoring and extended washout period.
The birth plan can be arranged flexibly.
The latest published results of the 2021 AAN conference show that dimethyl fumarate and flushing are at a higher risk.
Significantly related
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Common adverse reactions are mainly mild to moderate, and the safety is controllable
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Safety data for more than 10 years shows that the safety of dimethyl fumarate is controllable.
At any point in time, the incidence of infections, serious infections, gastrointestinal adverse events, MS recurrence, flushing, and nausea has not increased.

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The burden of monitoring the initial medication of dimethyl fumarate is small, and the occurrence of adverse events can be avoided as much as possible through regular monitoring
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Its active metabolite monomethyl fumarate (MMF) has a half-life of about 1 hour.
Most people do not have circulating dimethyl fumarate in the body after 24 hours.
There is no need to extend the washout period, which is convenient for women of childbearing age to flexibly formulate pregnancy Plan and adjust the treatment plan (Figure 9)
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Figure 9 Monitoring of the initial medication of dimethyl fumarate.
Fampridine sustained-release tablets provide a breakthrough treatment for patients with walking disorders.
MS treatment not only needs to pay attention to long-term disease management, but also needs to pay attention to the improvement of current dysfunction
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Walking dysfunction is very common in MS patients.
Up to 58% of patients report some mobility problems in the first year after MS is diagnosed; after 10 years, the proportion of patients is as high as 93%; 70% of patients with walking difficulties said This is the most challenging aspect of MS, affecting all aspects of the patient's physical and mental life
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1.
Fampridine sustained-release tablets is the first and currently the only drug approved to improve walking dysfunction in MS patients.
China has always lacked effective treatment methods for improving walking dysfunction suitable for various stages of MS
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Fampridine’s marketing can be said to be a zero breakthrough.
Fampridine sustained-release tablets are the world’s first and currently the only drug approved to improve MS walking dysfunction (EDSS 4-7).
It can be used alone or in combination with DMT.
Medications, physical therapy, and other symptomatic therapies are used for all subtypes of MS patients
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2.
Fampridine sustained-release tablets can effectively improve the walking ability of MS patients with good safety.
A number of RCT and real-world research data have confirmed that Fampridine can significantly improve the walking ability of MS patients and increase the walking speed of patients
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In the phase III clinical trial F203/204, the proportion of patients who responded to Fampridine sustained-release tablets treatment with T25FW (timed 25-foot walk) improved was 38%, which was significantly better than the placebo group (Figure 10)
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Figure 10 Phase III clinical trial F203/204 research results At the same time, the summary analysis of F203/204 showed that no matter what type of MS, whether or not DMT drugs are used or what DMT drugs are used, Fampridine can significantly improve the patient's T25FW walking response rate ( Figure 11)
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Figure 11 The results of the Phase III clinical trial F203/204 In addition, Fampridine is safe, most AEs are mild to moderate in severity, usually do not lead to treatment termination, and no new adverse events are observed after long-term treatment Or trend
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In the end, Professor Guan Yangtai concluded that although dimethyl fumarate has just been listed in China, it has more than ten years of experience in the world
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And studies have shown that long-term use has good efficacy and safety
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It also emphasizes that the half-life of dimethyl fumarate is very short, which is conducive to elution, which increases the convenience of medication for MS patients, especially female patients of childbearing age
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Fampridine is a symptomatic treatment to improve walking dysfunction in MS patients, especially for patients with EDSS 4-7, which has significant benefits
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The launch of two innovative products, dimethyl fumarate enteric-coated capsules and fampridine sustained-release tablets, has changed the pattern of MS treatment in China, and will provide a comprehensive treatment plan for the MS field to reduce disease-causing progress in the long-term and improve walking ability in the short-term.
, Provides a powerful tool for Chinese doctors to treat MS, and brings more treatment options to patients
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