​Professor Zhang Wen: There are endless calls, when will these "potential stocks" be approved for Sjogren's syndrome indications?

*It is only for medical professionals to read and refer to.
It is expected that the drug for the treatment of Sjogren’s syndrome will be approved as soon as possible to fill the gap in the field
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Primary Sjogren’s syndrome (pSS) is a common disease in rheumatology and immunology.
It mainly affects exocrine glands, causing symptoms such as dry mouth and eyes.
It can also be accompanied by features of extraglandular diseases, such as joints, skin, and kidneys.
And lungs, etc.
, system damage occurs
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Patients with pSS who go to the clinic often have different clinical manifestations and different treatment needs
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At present, no drugs with definite curative effect have been approved for pSS treatment, which makes it difficult for many doctors and patients.
How to choose drugs reasonably? How is the research progress of therapeutic drugs? When can drugs with pSS indications be used.
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In this issue, we are fortunate to invite Professor Zhang Wen from Peking Union Medical College Hospital to talk with us about the current status, progress and future prospects of the pSS treatment field
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Is there medicine or no medicine? Professor Zhang Wen has a wealth of clinical diagnosis and treatment experience in the field of pSS.
She said that pSS is a highly heterogeneous disease.
The clinical manifestations of patients vary in severity.
The milder only has local symptoms of dry mouth and eyes, while the more severe System involvement and organ damage occur
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In the process of clinical diagnosis and treatment, both doctors and patients have different concerns: patients often focus on the relief of symptoms, hoping that treatment can alleviate their physical discomfort as soon as possible; while doctors have different considerations for the overall treatment of the disease It is often necessary to comprehensively evaluate the patient’s basic personal conditions, symptoms, and disease progression, so as to formulate a more targeted treatment plan
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When talking about the current status of clinical treatment, Professor Zhang Wen pointed out that “pSS cannot be cured, but through standardized treatment, we can control the disease, delay the progression of the disease, and improve the overall quality of life of patients
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"The current treatment of pSS is divided into local treatment and systemic treatment
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Local treatment is mainly for dry mouth and dry eyes.
According to different levels of symptoms (such as mild, moderate and severe), different types will be given in the clinic.
Treatments include drugs to stimulate gland secretion, alternative therapies such as artificial saliva or tears, and cyclosporine eye drops; while systemic treatments include glucocorticoids, immunosuppressants, and biological agents [1]
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Professor Zhang Wen A detailed introduction to these categories of systemic treatment drugs: Glucocorticoids: generally used for patients with system damage and the disease is active
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The
dosage and course of treatment are adjusted according to the condition, and in principle, under the premise of effective control of the condition, the May be used in a short course and low dose to reduce its adverse reactions; immunosuppressive agents: There are many types of traditional immunosuppressive agents, including hydroxychloroquine (HCQ), methotrexate, leflunomide, iguratimod (IGU), Azathioprine, mycophenolate mofetil, calcineurin inhibitors, cyclophosphamide, etc.
, as well as plant drugs, including total glucosides of paeony and tripterygium wilfordii, are currently used in patients with pSS, but There is no indication for pSS
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The experience of clinical application is that different types of drugs are selected according to the patient’s condition and the affected organs
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According to the statistical results of the Chinese Systemic Lupus Erythematosus Research Cooperation Group (CSTAR), HCQ is currently in China The most widely used, many doctors choose HCQ as the first choice for the treatment of pSS system, but the clinical trials of HCQ treatment of pSS did not reach the research endpoint, suggesting that it has limited symptom relief of pSS [2]; biological agents: in recent years, targeting B cells, Biological agents such as costimulatory signals and cytokines are gradually being tried and clinically tested in pSS
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At present, they are mainly used in patients with poor results of conventional treatment, and the relevant clinical evidence is still insufficient
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Although there are many types of clinical drugs, Professor Zhang Wen said At present, the treatment of pSS is far behind other common rheumatic diseases
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"We have not yet approved drugs for pSS indications.
Most of the drugs currently used in the clinic are based on the treatment of other rheumatic diseases or empirical treatments.
These drugs lack high-level treatment in the field of pSS.
Evidence-based medicine
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” At this level, the field of pSS treatment is still facing a situation where there is no cure
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Continue to explore drugs with therapeutic potential, and realize the breakthrough of "from scratch" as soon as possible.
In order to break the incurable situation in the field of pSS, many studies are actively exploring potential therapeutic drugs
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As the mechanism of disease becomes clearer, there are more and more explorations of the efficacy of biological agents and targeted agents
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Excessive activation of B cells is the core of the pathogenesis of pSS.
The classic B cell-targeted biologics beliyuumab and rituximab combination therapy for pSS have been studied, but the results have not been officially announced (NCT02631538)
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In addition, Professor Zhang Wen also mentioned the related studies of CD40 monoclonal antibodies and B cell activating factor (BAFF) receptor blockers.
The results of the current phase 2 clinical studies show their good efficacy prospects [3-5], more The Phase 2, Extended Phase and Phase 3 studies are still in progress
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In addition, the mechanism of action of interferon pathway, interleukin-17 pathway and other target molecules in pSS also provides new ideas for the exploration of clinical therapeutic drugs, and related research is expected to bring many treatment options
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In addition to biological agents, research and exploration on traditional immunosuppressants are also in full swing
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Among them, China's self-developed category 1.
1 innovative drug IGU has attracted attention in recent years in the clinical research and potential application value of the domestic pSS field
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Professor Zhang Wen introduced that IGU is a disease-improving anti-rheumatic drug (DMARD) with a multi-target mechanism of action.
It is currently mainly used for the treatment of RA in clinical practice.

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It has B cell regulation and down-regulates the level of immunoglobulin [6], so it is expected to become one of the drug candidates for the treatment of pSS
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Many domestic hospitals have successively carried out prospective clinical studies
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Existing research results have shown that IGU can effectively improve the disease activity and various efficacy indicators of patients with pSS, and help alleviate their systemic involvement [7-15]
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More research on the treatment of pSS with IGU is still in progress, such as the Phase 2 study (NCT04830644) to evaluate the efficacy and safety of IGU and placebo in patients with pSS, and compare the efficacy and safety of IGU and HCQ in the treatment of pSS Phase 4 study (NCT04981145) and so on
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The publication of these research results will further reveal the therapeutic potential of IGU in this field
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So, with so many drugs under development, who is most likely to be the first to be approved for pSS indications? Professor Zhang Wen said that clinical research has great variables.
In the past, in the research field of SLE, many clinical trials of biological agents failed to reach the main research endpoints, and clinical research in the field of pSS will only be more difficult, because there is still a lack of effective and clear It is far from enough to understand the disease as an indicator that reflects the therapeutic effect
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Before convincing research results come out, it is difficult for us to predict this problem
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Of course, Professor Zhang Wen also believes that many drugs currently under research have therapeutic potential.
I believe that in the near future, we can obtain more beneficial information and more new drugs will enter this field
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The future is far away, but the future can be expected! Although there are no approved drugs for pSS indications, we can still effectively control the patient's condition through standardized treatment
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The Sjogren's Syndrome Group of the Rheumatology and Immunology Physicians Branch of the Chinese Medical Physician Association issued the "Primary Sjogren’s Syndrome Diagnosis and Treatment Specifications" in 2020, which provides many guiding opinions for the diagnosis and treatment of pSS in the clinic by rheumatology immunologists[1 ]
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Professor Zhang Wen pointed out that in clinical practice, we must first follow its most basic diagnosis and treatment norms, and then conduct individualized treatment on this basis
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With the in-depth understanding of disease pathogenesis in the future and the development and application of more drugs, pSS will develop in the direction of stratified treatment and precise treatment, that is, according to classification methods such as clinical phenotype and immunophenotype, different patients Appropriate and targeted treatments are given to maximize the benefits of patients and minimize adverse reactions
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Professor Zhang Wen said that although it is still difficult to achieve the above treatment goals, many ideas seem remote
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But this is a very useful direction for exploration, and it is also a direction we will strive to achieve in the future
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Continue to explore and study, the future is promising
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Summary: The standardized diagnosis and treatment of pSS lags behind other common rheumatic diseases.
Although there are many kinds of drugs in the clinic, most of the drugs have poor efficacy and lack high-level evidence-based medical evidence.
There is no approved indication for this indication.
Drugs
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At present, many researchers are committed to the development of drugs for the treatment of pSS, some of which have achieved phased results and are expected to further expand in this field
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We look forward to the emergence of drugs with pSS indications in the near future, and especially look forward to the benefits of drugs developed independently by my country to benefit patients! Expert profile Professor Wen Zhang, deputy director of the Department of Rheumatology and Immunology, Peking Union Medical College Hospital, member and secretary of the Chinese Rheumatology Branch, a doctoral supervisor Visiting scholars from Harvard Medical School and NIH have undertaken a number of national and Beijing Natural Science Foundation projects.
References: [1] Zhang Wen, Li Xiaomei, Xu Dong, etc.
Standards for diagnosis and treatment of primary Sjogren’s syndrome[J].
Journal of Internal Medicine, 2020,59(4):269-276.
[2]Fox RI,Fox CM,Gottenberg JE,et al.
Treatment of Sjögren's syndrome:current therapy and future directions[J].
Rheumatology(Oxford).
2021, 60(5):2066-2074.
[3]isher BA,Szanto A,Ng WF,et al.
Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome:a multicentre, randomised,double-blind,placebo- controlled,proof-of-concept study[J].
Lancet Rheumatol.
2020,2:e142–e152.
[4]Dörner T,Bowman SJ,Fox R,et al.
OP0302 Ianalumab(VAY736),a dual mode of action biologic combining BAFF receptor inhibition with B cell depletion, reaches primary endpoint for treatment of primary Sjögren's syndrome[J].
Ann Rheum Dis.
2020,
.