The ideal disease-modifying drug for multiple sclerosis under the new crown epidemic, have you chosen the right one?

*Only for medical professionals to read and refer to a reasonable selection of drugs to help MS patients safely pass the special period.

Multiple sclerosis (MS) is an immune-mediated disease characterized by central nervous system (CNS) inflammatory demyelinating disease.
The disease mainly involves white matter.
Common symptoms include decreased vision, diplopia, limb sensory disorders, Limb movement disorders, ataxia, bladder or rectal dysfunction, etc.

The etiology is not yet clear, and may be related to multiple factors such as genetics, environment, and viral infections [1].

80% to 85% of MS patients showed relapsing-remitting type in the initial course of the disease, that is, there is an obvious relapse and remission process, but 50% of the patients no longer have relapsing and remission after 10-15 years of the disease, showing a slow Progressive aggravation [1].

In the remission phase of MS, disease modification therapy (DMT) can reduce the frequency of patient relapses, reduce the degree of deterioration, delay the natural progression of the disease and improve the prognosis of patients [2].

The outbreak of the new coronavirus pneumonia (hereinafter referred to as "new crown pneumonia") at the end of 2019 has had a major impact on people's lives.

With the repeated outbreak of the new crown, will MS patients have an increased risk of contracting new crown pneumonia? How should DMT be managed under the epidemic? Let us understand the current infection risks faced by MS patients and the corresponding treatment strategies.

Under the new crown epidemic, MS patients need to be cautious when using drugs.
Because DMT drugs can affect the immune system to varying degrees, it is internationally believed that the use of certain DMT drugs may increase the risk of MS patients contracting new coronary pneumonia [3].

Previous studies have shown that the aggravation of MS is related to viral infection.
Infection of the virus in MS patients may accelerate the progression of the disease, and the probability of disease deterioration in patients with relapsing MS after infection with the virus increases by 2-3 times [4].

Therefore, under the new crown epidemic, clinicians need to fully assess the infection risk of MS patients and formulate individualized treatment strategies.

For MS patients, especially patients receiving DMT drug treatment, many MS academic organizations have issued guidelines for MS and DMT management under the epidemic.

The MS International Federation emphasizes that all MS patients should pay special attention to reducing the risk of new coronary pneumonia infection, especially elderly MS patients who suffer from heart and lung diseases at the same time, and their exposure to the new coronavirus should be minimized [5].

Regarding the DMT strategy for MS patients in the new crown epidemic, the National MS Association pointed out that DMT drug treatment should be continued, and the relevant risks should be discussed with the doctor in charge before DMT drugs are stopped [6].

For patients infected with new coronary pneumonia, the British Association of Neurologists recommends that all injection and oral DMT drugs be stopped [7].

According to the guidelines of the British Association of Neurologists, in the new crown epidemic, drugs that can be used safely include interferon β1a, interferon β1b, teriflunomide, glatiramer acetate and dimethyl fumarate.

Because these drugs increase the risk of viral infections very slightly, and are far less than the risk of recurring disease.

Although some people think that the total lymphocyte count can be used to predict the risk of viral infection, the literature is not clear, so it is not recommended to make any changes to the current monitoring guidelines for these drugs [7].

Teriflunomide does not increase the risk of infection in MS patients, a safe choice! Among the DMT drugs recommended by international guidelines that can be used safely under the new crown epidemic, teriflunomide is a small molecule oral drug.

Because teriflunomide selectively inhibits the proliferation of activated lymphocytes while retaining the protective immune response of resting lymphocytes, it will not cause severe immunosuppression [8-9].

A pooled analysis of the safety data of four studies of teriflunomide (1 phase II study and 3 phase III studies) showed that neutrophil and lymphocyte counts decreased by <15% during treatment with teriflunomide and maintained In the normal range, it is proved that the use of teriflunomide does not increase the risk of infection in MS patients [10].

Figure 1 Neutrophils and lymphocytes maintained in the normal range during teriflunomide treatment.
MS patients treated with DMT drugs need to be cautious about vaccination.
Vaccination is an important measure to prevent and control infectious diseases.

According to the production process and virulence, vaccines can usually be divided into live attenuated vaccines and inactivated vaccines.
The former has a certain risk of restoration of virulence, and the latter is non-infectious and relatively safe [11].

Studies have shown that MS disease itself usually does not affect the effectiveness of vaccination, and vaccination does not cause the development and deterioration of MS [12].

The American Academy of Neurology’s MS Infection and Vaccine Practice Guidelines point out that the use of vaccines to prevent infection is a key part of MS patients’ health care.
MS patients should be vaccinated according to standard vaccination guidelines, but before any vaccines, the patient’s current status should be considered MS treatment drugs being used [13].

At present, there are only three oral DMT drugs in China.
Due to different mechanisms of action, the requirements for vaccines are also different.
Therefore, MS patients during DMT treatment should be cautiously vaccinated with live attenuated vaccines and inactivated vaccines, and should actively consult MS treating doctors.

Table 1 Precautions related to vaccination of three domestic oral DMT drugs A multi-center, parallel group design study included 122 patients who received teriflunomide (79 cases) or IFNβ-1 (43 cases) for at least 6 months Patients with relapsing MS were vaccinated with the 2011/2012 inactivated seasonal influenza vaccine containing H1N1, H3N2 and B strains.
The main study endpoint is the proportion of patients with influenza strain-specific antibody titers ≥40 28 days after vaccination.

The results of the study showed that the response of patients receiving teriflunomide to the seasonal influenza vaccine vaccinated meets the European Medicines Agency's standard that the proportion of 18-60 year-old vaccinators with antibody titer ≥40 needs to reach 70%, and it is safe Good sex and tolerability.

The study provides level II evidence that teriflunomide does not negatively affect the immune response of patients with relapsed MS vaccinated with inactivated influenza vaccine [17-18].

Figure 2 Patients receiving teriflunomide can produce an effective immune response to seasonal influenza vaccination.
There are no clinical data on the efficacy and safety of live vaccination patients taking teriflunomide, so it is recommended not to vaccinate live vaccines [14].

At present, the four human papillomavirus (HPV) vaccines approved in my country are all recombinant protein vaccines, based on virus-like particles (VLP) formed on the surface of HPV virus, do not contain viral DNA and are not infectious[19-22 ].

Teriflunomide is unlikely to affect the HPV vaccine.

At present, there are many new crown vaccines on the market in China, and all the new crown vaccines for key populations are inactivated vaccines [23].

Teriflunomide does not affect the effectiveness of inactivated vaccines, so MS patients can be vaccinated with inactivated new crown vaccines.

Summary MS is a lifelong disease.
The main goal of remission treatment is to control the progression of the disease.
The current guidelines recommend the use of DMT therapy.

Because some DMT drugs can affect the immune system of patients and increase the risk of patients with new coronary pneumonia, multiple guidelines have been issued internationally to guide current MS treatment.

Among the DMT drugs that can be used safely under the epidemic situation recommended by the guidelines, teriflunomide does not cause severe immunosuppression, does not increase the risk of infection, and does not affect the effectiveness of inactivated vaccination.

At the same time, as an easy-to-use oral drug, teriflunomide is undoubtedly an ideal choice for DMT in MS patients under the new crown epidemic! Expert profile Professor Dong Huiqing Chief physician, professor, and doctoral tutor of Xuanwu Hospital of Capital Medical University • Current work unit Department of Neurology, Xuanwu Hospital, Capital Medical University, as the head of the immunological disease professional group of the Department of Neurology • Consultant of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association • Deputy Director of the Neuroimmunology Branch of the Chinese Society of Immunology • Associate of the Neuroimmunity Professional Committee of the Society of Neurology of the Chinese Medical Doctor Association Chairman•Deputy Chairman of the Special Committee of Stroke Immunity of Chinese Stroke Society•Associate Editor of Chinese Journal of Neuroimmunology and Neurology•Main Research Fields: Nervous System Inflammation and Immunological Diseases (such as encephalitis, demyelinating disease, acute and chronic inflammatory Nerve root neuropathy, etc.
).

Published more than 90 papers in statistical source journals and 4 in SCI.

• The project once undertaken by the Ministry of Health in the "Ninth Five-Year Plan" of the "Early Clinical Diagnosis of Alzheimer's Disease" project, the current research project "Autologous Hematopoietic Stem Cell Transplantation Treating Multiple Sclerosis Long-term Clinical Efficacy" And Imaging Research", "Diagnosis of Multiple Sclerosis by T-cell Receptor Vβ Chain Structure Determination of the Capital Citizen Health Cultivation Project of Beijing Municipal Science and Technology Commission", etc.

[22] Jiadaxiu 9 instructions.
[23] What is the difference between the new coronavirus inactivated vaccine and the mRNA vaccine? a) http: //health.
people.
com.
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