Professor Zeng Xiaofeng: Can the exploration of targeted therapy improve the "less drug" situation in SLE?

*It is only for medical professionals to read and refer to.
Nowadays, different from the past, SLE treatment methods are becoming more abundant
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Although the wolf is an extremely ferocious animal, human history has proved that the wolf can be domesticated
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Systemic lupus erythematosus (SLE) is like a fierce and sinister wolf, threatening human health and even devouring the lives of patients
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But just like the wolf in the animal kingdom, SLE can also be controlled
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In order to further understand the characteristics of the disease, the current status of treatment and treatment methods, we invited Professor Zeng Xiaofeng, the director of the Department of Rheumatology and Immunology of Peking Union Medical College Hospital, to answer us about two or three things about the diagnosis and treatment of lupus
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Professor Zeng Xiaofeng’s interview video.
You shared the content of the "2020 China Systemic Lupus Erythematosus Development Report" in the academic annual meeting of the Rheumatology Branch, which introduced the latest epidemiological data, clinical features, and diagnosis and treatment status of current SLE in China
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What kind of disease is SLE? What impact and burden may it cause to patients? Professor Zeng Xiaofeng: SLE is a classic autoimmune disease that can affect system and organs throughout the body
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There are millions of lupus patients in China.
Among the various races in the world, the incidence of SLE among Han people ranks second, and the number is huge [1]
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SLE is more common in women of childbearing age (15-45 years old) and poses a serious threat to the patient's physical and mental health and quality of life-it can cause multiple organ damage and dysfunction (such as kidney function and respiratory failure), and even lead to death
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The natural course of SLE is mostly manifested as the aggravation and remission of the disease alternately, so that it is prolonged and unhealed
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At present, there is no cure for the disease, and effective treatment is mainly used in clinical to help patients control and stabilize the disease
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Figure 1: Domestic epidemiological data of SLE, can you briefly introduce to us the current status of clinical treatment of SLE in China? Professor Zeng Xiaofeng: The treatment of SLE has always been in a state of "lack of medicines and doctors"
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On the one hand, the number of specialist doctors is small
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The diagnosis and treatment of SLE is complicated.
Unless professional training and practice are required, it is difficult for general medical workers to correctly diagnose and standardize the patient's condition; on the other hand, there are few drugs with SLE indications
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For half a century, only 5-6 drugs have been approved for the treatment of SLE.
Traditional therapeutic drugs such as hormones, antimalarials and immunosuppressants have not been satisfactory in controlling the disease.
Many patients still have relapses after treatment.
Seizures
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The approval of beliyuumab for the market has opened a new era of SLE biotherapy and improved the "less drug" situation to a certain extent
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This year, another new lupus drug, Tetazep, was officially approved for marketing in China, which has doubled our confidence
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At present, there are countless new drugs being developed in the field of SLE, and treatment methods are becoming more and more abundant.
It is believed that with the development and application of these innovative drugs, the situation of SLE treatment will be further improved
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Figure 2: Conventional treatments have limitations and biologics have become a new treatment method.
Based on your many years of clinical experience, what do you think are the focus and difficulty of current SLE treatment? How can we better break through the key points and difficulties of treatment? Professor Zeng Xiaofeng: After standard treatment, most patients with SLE can be well controlled, but this does not mean that everything will be fine since then
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The course of SLE is mostly an alternating process of recurrence and remission.
Repeated attacks cause the body's antigen-antibody complexes to continuously deposit in various tissues and organs, which can cause multiple organ damage
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How to effectively reduce recurrence and organ damage, and improve the prognosis of patients, is the current challenge in the clinical treatment of SLE
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In the "2020 China Systemic Lupus Erythematosus Diagnosis and Treatment Guidelines", we proposed the standard treatment of SLE and clarified the treatment goals for disease control activities [2]
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Figure 3: "2020 China Systemic Lupus Erythematosus Diagnosis and Treatment Guidelines" According to our current understanding of the disease mechanism, B cells are an important factor in the progression of SLE disease, and therapeutic strategies targeting B cells have attracted much attention
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What do you think about the application of therapeutic strategies targeting B cells in the treatment of SLE? Professor Zeng Xiaofeng: SLE is an autoimmune disease that spreads widely in the immune system
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Current research evidence shows that B cells, T cells and other types of immune cells are involved in the occurrence of diseases
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Our marketed biologics and many drugs under research use B cells as therapeutic targets.
The clinical therapeutic effect has been affirmed.
There is abundant evidence-based medical evidence in reducing disease activity, organ damage, and recurrence.
B cells do play a central role in the pathogenesis of SLE
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Figure 4: B cells are the key link in the pathogenesis of SLE.
At present, there are three main biologics targeting B cells on the Chinese market: beliyuumab, tetaxel and rituximab, each of which is different: Liuximab is an inhibitor of B lymphocyte stimulating factor (BLyS), which inhibits the proliferation and differentiation of B cells, resulting in a decrease in B functional activity; tatacept is an inhibitor of BLyS and proliferation-inducing ligand (APRIL).
The dual targets more completely inhibit the B cell pathway; Rituximab is an anti-CD20 monoclonal antibody that works through B cell clearance.
Although the application has high safety risks (such as infection) and has not been approved for SLE indications, It still has an important therapeutic effect in refractory cases
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Relatively speaking, the safety risks of belyumumab and taltacept are relatively small, which is conducive to the balance of benefits and risks in treatment
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Figure 5: The overall goal of B cell targeted drugs: to block the key pathway for plasma cell differentiation and development.
In addition, the activation of the type I interferon (IFN) pathway is also an important pathogenic factor for SLE, but the type I targeted this pathway IFN receptor antagonists are currently only available in the United States and have not yet been approved for use in China
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T cells are also a promising therapeutic target.
Although there is no approved relevant treatment method yet, a large number of relevant studies are already in progress
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Why is my country's self-developed lupus new drug Tetazep so quickly approved for marketing? Can its application help us overcome the focus and difficulty of current SLE treatment? Professor Zeng Xiaofeng: The two currently approved biologics-belyumumab and tytacept, clinical studies have shown their good efficacy, can well control SLE disease activity, reduce disease recurrence and organ damage [3-6]
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Compared with a single target, Taltazep can simultaneously inhibit two B-cell related cytokines: BLyS and APRIL.
Therefore, in principle, it can not only inhibit the further development and maturation of immature B cells, but also inhibit mature B cells.
The differentiation of cells into plasma cells affects the production of autoantibodies to abnormal plasma cells, which can more completely inhibit the B cell pathway and have a stronger effect
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At present, these two biologics have been in clinical application for a short period of time, and we look forward to further accumulation of clinical data
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Figure 6: Taltazep's mechanism of action Based on the current research status of Taltazep, what are your expectations for its future development? Professor Zeng Xiaofeng: China has the most SLE patients in the world, and there is a great demand for treatment
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Taltazep is a domestic biological agent.
Its listing is not only a great achievement in the field of SLE research, but also a boon for Chinese patients with SLE, which will bring them more benefits
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Whether it is from an economic or sociological point of view, Thatasep will play a huge role
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Expert profile Professor Zeng Xiaofeng, Director of the Department of Rheumatology and Immunology, Peking Union Medical College Hospital, PhD student/postdoctoral supervisor, Director of the National Center for Clinical Research on Dermatology and Immunological Diseases, Vice Chairman of the Asia-Pacific Association of Rheumatology (APLAR), Executive Director of the Chinese Medical Doctor Association and Rheumatology and Immunology Branch President, Chinese Medical Association Rheumatology Branch, Former Chairman, Chinese Immunological Society, Vice Chairman, Chinese Society of Immunology, Clinical Immunology Branch, Vice Chairman, Chinese Society of Rehabilitation Medicine, Bone, Joint and Rheumatology Branch, Standing Director, Cross-Strait Medical Exchange Association, Standing Director, Beijing Medical Association and Honorary Chairman of the Rheumatology Professional Committee China Systemic Lupus Erythematosus Research Collaboration Group (CSTAR) and the head of the National Rheumatism Data Center (CRDC)
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EUSTAR (EULAR Scleroderma Trials and Research, EUSTAR) China Center Leader Reference [1] Chinese Medical Association Rheumatology Branch.
Chinese Journal of Rheumatology.
2010; 14(5):342-346.
[2] Zeng Xiaofeng.
Chinese Journal of Internal Medicine.
2020,59(3): 172-185.
[3]Felten R, et al.
Autoimmun Rev.
2018;17(8):781-790.
[4]Zhang F, et al.
Ann Rheum Dis 2018;77:355–363.
[5]Wu D, et al.
Arthritis Rheumatol.
2019; 71 (suppl 10).
ABSTRACT NUMBER: L18.
[6]Navarra SV, et al.
The Lancet, 2011, 377(9767 ): 721-731.
*This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position
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