I don’t know how to distinguish between silly, and there are so many types of multiple sclerosis, how to choose the medicine?

*Only for medical professional knowledge and reference to select drugs according to the individualized situation of multiple sclerosis patients to help patients return to normal life as soon as possible.

"A Hundred Meters in Life" is an inspirational and funny Spanish film.
Ramon, who has a perfect life and family, is expecting the birth of his second child.
At this time, the doctor told him that he was suffering from the rare "multiple sclerosis" (MS).
, And had begun to become ill, and soon he couldn't even walk a distance of 100 meters.

But Ramon did not abandon himself because of the illness, but with the encouragement of his family, worked hard to cooperate with the treatment, and finally completed the triathlon challenge miraculously.

(Big coffee explains MS) Although this is a film adapted from real events, in fact, there are many people in our lives whose perfect lives may be completely changed by a disease like MS.

MS is a serious, lifelong, and progressive central nervous system disease.
Most patients have their first symptoms between 20-40 years old.
It is one of the most common causes of neurological disability in young adults.

Up to now, MS is still incurable, but fortunately, MS is not an incurable disease, and early initiation of treatment can effectively delay the progression of the disease [1].

As the saying goes, the nine sons of the dragon are different.
Before starting treatment, we have to figure out the type of the disease and prescribe the right medicine.

PART 01MS disease classification, do you really understand? The clinical classification of newly diagnosed MS patients can be divided into clinical isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and primary according to the severity of the disease.
Progressive multiple sclerosis (PPMS), different types of patients have different characteristics: CIS: in line with the first onset of MS, 85% of MS patients start with CIS [2-6]; RRMS: manifested as an obvious recurrence and remission process , Basically recovered after each attack, leaving no or only minor sequelae.80%~85% of MS patients present this type during the initial course of disease [6]; SPMS: recurrence is reduced, disability progresses slowly, and about 50% of RRMS patients develop SPMS after 10 to 15 years of illness [6]; PPMS : The course of the disease is more than 1 year, and it is slowly progressively worsening, and there is no remission and recurrence process.
About 10% of MS patients present this type [6].

Figure 1: Changes in the degree of disability of different subtypes of MS over time [7] According to the latest "Blue Book of Health Insights on Patients with Multiple Sclerosis in China and the 2021 Quality of Life Report on Patients with Multiple Sclerosis in China" released in 2021, the current CIS, RRMS, and SPMS The ratios of PPMS and PPMS in MS patients in my country are 14.
1%, 78.
2%, 5.
1% and 2.
6%, respectively.
RRMS is the most common MS type [8].

But in fact, RRMS can be further classified.

So, what are the characteristics of different patients and how should they be treated? PART 02 focuses on the largest population of RRMS patients, get treatment points! Clinically, RRMS patients can be divided into benign type (4%~5%), general activity (80%~85%), high recurrence (HAMS) and rapid progression type (RES-RRMS) (both 10%~ 15%) [9].

▌ Patients with benign MS At present, the criteria for judging benign MS are actually not clear.

The 2019 MS Center Consortium (CMSC) Disease Modification Therapy (DMT) Drug Selection Practice Guide proposes that benign MS is a retrospective diagnosis with a very low incidence, and there are few signs at the onset of MS to indicate which patients may have a benign course[ 9].

In view of the fact that MS patients who give up or delay DMT treatment will face the risk of worsening their condition without DMT, the term benign MS should be used with caution in clinical practice.
It is recommended not to try to predict benign MS and to give up or delay DMT treatment accordingly.
Initiate first-line DMT therapy [9,10].

▌ General active RRMS General active RRMS accounts for the largest proportion in the population.
Among RRMS patients, except for benign MS, HAMS, and RES-RRMS, all patients belong to this type, and no special definition is required. At present, for patients with general active RRMS, advanced treatment strategies can be selected [11].

The basic principle of advanced treatment is based on the use of safe and effective drugs to start treatment as soon as possible.
It has good safety and can enable many patients to achieve satisfactory disease control while receiving relatively safe drugs without having to upgrade to a higher level.
It is a second-line DMT drug [12-14].

Figure 2: Advanced treatment options and the division of first and second line drugs [15-17] ▌ HAMS currently has different definitions of HAMS, which may include measurement of recurrence and MRI disease activity, such as data on gadolinium-enhanced lesions.

Therefore, there is no consensus on the treatment of HAMS, but in view of the fact that HAMS patients have not yet progressed to the stage of continuous progression of disability dominated by irreversible nerve damage, clinical drug selection needs to take into account both efficacy and safety [18,19].

▌ RES-RRMS2018 British National Medical Service (NHS) DMT treatment plan defines RES-RRMS, that is, the patient has ≥2 disabling recurrences within 1 year, and the brain MRI has ≥1 gadolinium-enhanced lesions or T2 lesions The load has increased significantly compared to before.

For such patients, the 2018 NHS DMT recommends rescue treatment starting from the posterior DMT [18].

Figure 3: The treatment recommendation for patients with RES-RRMS in the 2018 NHS DMT treatment plan PART 03, the first oral DMT in China, suitable for a wide range of MS populations.
Teriflunomide was approved for listing in China in July 2018 and is China’s treatment for MS The first oral first-line DMT drug.

Teriflunomide is suitable for the treatment of adult relapsing MS, including CIS, RRMS and active SPMS, covering a wide range of MS patients in the clinic.
There have been multiple studies that have confirmed its efficacy in different populations: ▌ CIS Teriflunomide is currently the only oral DMT drug with CIS Phase III clinical research evidence in China.
Its TOPIC study shows that: 14mg teriflunomide treatment can reduce the risk of CIS patients progressing to clinically confirmed MS (CDMS) due to recurrence.
At the same time, it can reduce the recurrence risk of MRI (that is, the risk of new lesions visible on MRI) by 35% [20]. Figure 4: Results of the core TOPIC study of teriflunomide in the treatment of CIS▌ RRMS In patients with general active RRMS, a number of core studies such as TEMSO and TOWER studies have confirmed that teriflunomide can control the development of the disease in multiple ways, including reducing the recurrence rate , Persistent disability progression risk and MRI lesion activity, and slow down brain atrophy.

It is particularly worth mentioning that in the real world research data in China, the data of teriflunomide is better, which can significantly reduce the annual recurrence rate (ARR) of Chinese MS patients by 71.
2% [21-24].

Figure 5: The core study results of teriflunomide in the treatment of patients with general active RRMS.
Similar results were also observed in HAMS patients.
Compared with placebo, first-line DMT teriflunomide significantly reduced ARR and delayed the progression of disability in patients with HAMS [25 ].

▌ The follow-up study of active SPMSTEMSO for up to 9 years and TOWER for up to 5.
5 years analyzed 122 cases of active PMS patients treated with teriflunomide (including SPMS and PRMS-PRMS is progressive relapsed MS and is no longer used at present This classification) long-term prognosis [26,27].

The results showed that teriflunomide can effectively control the disability progression of patients with active SPMS, and 80.
3% and 83.
6% of patients did not have confirmed disability progression at 12 and 24 weeks, respectively.

In addition, despite the high baseline Extended Disability Status Scale (EDSS) score (median 4.
0) of patients, most patients still have EDSS scores below 6 points or less in 12 weeks or 24 weeks or even longer.
The threshold of 7 points.

Summary The condition of MS is complex and involves a variety of disease types.
Therefore, when choosing DMT treatment drugs for MS patients, multiple factors must be considered comprehensively, following the principle of individualization, and selecting according to different types of diseases.

Teriflunomide has a wide range of indications.
It is effective for patients with high-risk CIS, general active RRMS, high recurrence HAMS, and active SPMS.
It is the first-line preferred DMT for these patients. References: [1] "2020 Comprehensive Social Survey Report on Patients with Multiple Sclerosis in China" released.
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*It is only used to provide scientific information to medical professionals and does not represent platform views