Professor Liu Huaxiang | Encountered "violation" by rigidity?

*Only for medical professionals to read for reference, not without medicine! Ankylosing spondylitis (AS) is no longer a strange disease to us.
It is a relatively common autoimmune disease in rheumatology and immunology.
It mainly affects the body’s "weight-bearing column" (spine) and joints, which can cause The patient has low back pain, stiffness, and limited mobility.

In the past, due to the lack of treatments, many patients' conditions were not well controlled, and AS was even compared to "an undead cancer.
"
Today, with the development of various biomedical technologies, AS treatment has become relatively mature.

Today, we invited Professor Liu Huaxiang from Qilu Hospital of Shandong University to give us a detailed introduction to the current clinical AS treatment strategies and related research progress.

Gradually, the pathogenesis has been innovatively discovered that AS is an autoimmune disease, and its pathogenesis is quite complicated, and it is still not fully elucidated.

In recent years, there have been many breakthroughs in the research on the pathological mechanism of AS, which provides us with a new theoretical basis for revealing the deeper pathogenesis of AS and optimizing the existing diagnosis and treatment methods.

At present, it is believed that the occurrence and development of AS are closely related to factors such as genetic, immune function disorders, and infections.

Genetic factors: The incidence of AS is closely related to HLA-B27.
90% of AS patients are HLA-B27 positive, which is much higher than the carrier rate of the normal population [1].

Abnormal HLA-B27 molecules may induce a series of autoimmune reactions in the body, causing the proliferation of Th17 cells and the increased expression of interleukin-23 (IL-23), IL-17, and interferon-γ (IFN-γ) [2]; Factors: Immune cells and cytokines are thought to play an important role in the pathogenesis of AS.

T cells (Th1, Th2, Th17 cells) and B cells can play a key role in the immune imbalance of AS, and the cytokines they release or regulate such as IL-17, tumor necrosis factor-α (TNF-α), IFN -γ is also involved in pathological processes such as inflammation, fat deposition or new bone formation in AS.

In addition, specific immune pathways such as IL-23/IL-17 pathway and NF-κB signaling pathway also play a regulatory role in the pathogenesis of AS [3-4]; in addition, prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2) also plays an important role in the pathophysiological process of AS.

COX2 and PGE2 are not only related to the occurrence of pain, but also promote the overactivity of bone formation through a series of complex intercellular interactions, causing the bone formation effect of osteoblasts to be greater than the bone resorption effect of osteoclasts, destroying bone formation and bone The dynamic balance of absorption eventually leads to bony rigidity [2].

Figure 1: Resident mesenchymal cells located at the attachment point express COX2 and prostaglandin G/H synthetase.
It is precisely because of the new discoveries of the above key targets, signal pathways and pathological mechanisms that we can achieve this during the treatment of AS Targeted, looking for drugs with a highly matched mechanism of action, and defeating the disease through different treatment strategies.

With each passing day, AS treatment methods are becoming more abundant.
When talking about the changes in AS treatment, Professor Liu Huaxiang told us that AS is not without medicine.
Although it cannot be cured, there are currently a variety of treatment drugs available in the clinic.
Control the symptoms of the disease, delay the condition, and meet the clinical needs of the vast majority of patients.

Immediately, Professor Liu Huaxiang gave a more detailed introduction to the different treatment drugs for AS.

At present, the drugs used for the treatment of AS are mainly non-steroidal anti-inflammatory drugs (NSAIDs) and biological agents.

Among them, NSAIDs are the first-line drugs for the treatment of AS.
They have anti-inflammatory and analgesic effects and can quickly relieve inflammation and pain, but they cannot well control the progression of the disease.

Professor Liu Huaxiang pointed out that in clinical treatment, NSAIDs are generally used in combination with other drugs such as disease-improving anti-rheumatic drugs (DMARDs), and NSAIDs alone are rarely used.

Moreover, NSAIDs require sufficient long-term use, but their common adverse reactions include gastrointestinal reactions, cardiovascular diseases, adverse renal reactions, and liver damage, which should cause widespread concern [5].

With the development of biomedical technology, innovative drugs such as biological agents continue to emerge.

Professor Liu Huaxiang pointed out that currently available biological agents for AS treatment are divided into two categories-TNF-α inhibitors and IL-17A inhibitors.

TNF-α and IL-17A are the key cytokines in the occurrence and development of AS.
Various biological agents regulate related pathological processes through targeted therapy, and have the advantages of high specificity, rapid onset of action and significant curative effect.

TNF-α inhibitors are the earliest biological agents used in the treatment of AS.
At present, a large amount of evidence-based medical evidence has been accumulated.
Their use can quickly and effectively alleviate disease symptoms and reduce disease activity, which greatly improves the treatment level of AS .

However, TNF-α inhibitors have increased the risk of tuberculosis infection and hepatitis B recurrence in patients, and their therapeutic applications in some patients are limited [6-7]; IL-17A inhibitors are a new type of biological agent developed in recent years .

In view of the fact that IL-17A plays an important role in the occurrence and development of AS, IL-17A inhibitors can comprehensively improve the status of AS treatment, which can not only relieve short-term symptoms, but also achieve long-term bone protection and function maintenance [8].

Professor Liu Huaxiang said that in the past, these biological preparations were expensive, and long-term medication has brought a huge economic burden to patients.

However, more and more biological agents with good curative effects have been included in the scope of medical insurance reimbursement, and their accessibility has been greatly improved.

The emergence and popularization of these innovative drugs have promoted the treatment of AS into the era of biologics, bringing new treatment options and hope for patients.

Figure 2: The treatment of spondyloarthritis (SpA) [9] never stops, and the treatment strategy for refractory AS needs to be optimized.
Although biologics have met the clinical needs of most patients, under the influence of many limiting factors, Not everyone can benefit from treatment with biological agents.

For some patients with refractory AS, the treatment strategy still needs to be optimized.

Therefore, the exploration and research of AS treatment drugs are still being constantly updated.

When it comes to the research progress of therapeutic drugs, Professor Liu Huaxiang said that small-molecule targeted drugs (such as JAK inhibitors) are gaining momentum, and many related studies are underway [10-12].

Blocking the JAK pathway may regulate a variety of key cytokines in the complex network, thereby exerting the effect of inhibiting inflammation and alleviating diseases.
This is a new way of thinking about applying it to AS treatment.

In addition, the traditional treatment of AS also has more room for optimization.

Although traditional synthetic DMARDs (csDMARDs) have not shown a clear effect on the symptoms of axial joints, and are not commonly used in AS treatment, when AS patients are accompanied by peripheral joint disease, considering the effective relief of csDMARDs in peripheral joint symptoms, a combination can be considered Use csDMARDs for treatment.

In addition, the use of traditional therapeutic drugs may alleviate the treatment dilemma of refractory AS to a certain extent.

Professor Liu Huaxiang introduced that in clinical practice, for some patients who do not respond well to biological agents, the combined use of traditional drugs may enhance the efficacy of biological agents.

If studies have found that TNF-α inhibitors combined with the new csDMRAD ilamod (IGU) in the treatment of AS patients can effectively improve their disease activity, regulate bone metabolism and the balance of the osteoprotegerin system, and their efficacy is significantly better than TNF-α Inhibitor monotherapy [13].

In addition, IGU can also be combined with NSAIDs to reduce the disease activity of patients and increase the ASAS response rate (Table 1) [14-19].

This shows that the combination of traditional therapeutic drugs is expected to further optimize the existing AS treatment strategies, and it is worthy of more in-depth research and exploration.

Table 1: Related research on the application of IGU in the treatment of AS [13-19] Summary: AS is not an "immortal cancer", modern science and technology are changing with each passing day, and we have made many important advances in the field of diagnosis and treatment.

Although AS treatment has entered a new era of biological agents, traditional treatment programs are still solid and reliable backing for patients, and there is room for further optimization.

We look forward to the further expansion and enrichment of AS treatment methods in the future, so that more patients can benefit from it.

 Expert Profile: Professor Liu Huaxiang, Chief Physician, Department of Rheumatology, Qilu Hospital of Shandong University, Associate Director of Department of Internal Medicine, Qilu Hospital of Shandong University, Professor of Shandong University, doctoral tutor, and doctor of medicine The 6th Shandong Province Top Ten Female Doctors as the project leader, presided over the National Natural Science Foundation of China 2 items, received 5 scientific and technological awards, published more than 50 academic papers in domestic core journals and international academic journals, of which more than 40 articles were included in the SCI, the executive director of the Chinese Rheumatology and Immunology Medical Association, the vice chairman of the Rheumatology Branch of the Shandong Medical Association Shandong Vice Chairman of the Society of Integrative Medicine, Shandong Society of Immunology, Vice Chairman of the Rheumatology Committee Reference Materials: [1] Bowness P.
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