Ankylosing spondylitis (AS) is a chronic inflammatory disease that can cause damage to the spine, hip, and sacroiliac joints, resulting in stiffness and pain in the neck, back, waist, and buttocks, and, in later severe cases, may lead to "fusion" of the joints, making them immobile.
According to statistics, AS is commonly seen in young people aged 16 ~ 30, male. Clinical data show that there are more than 5 million cases of AS patients in China, among which about 150-1 million patients have varying degrees of disability, and about 1/20 of them have caused severe disability.
The cause of AS is not very clear, but it is closely related to genetic factors and environmental factors. At present, there is no cure for AS, which is mainly used to relieve pain and stiffness, control and reduce inflammation, and reduce disease progression through surgery, drug and non-drug combined treatment.
However, with the deepening of people's understanding of AS and the constant change of diagnosis and classification criteria, AS treatment has entered the era of biological agents from the era of traditional drugs, and achieved a leap from 1.0 to 2.0 and then to 3.0 times.
Age 1.0
In the 1.0 era, namely the era of traditional therapeutic drugs, treatment mainly focused on symptom control.
Traditional treatment drugs include non-steroidal anti-inflammatory drugs (NSAIDs), hormones, traditional synthetic anti-rheumatic drugs (csDMARDs), among which NSAIDs are the main means to control symptoms.
The 2.0 Era
The 2.0 era, the tumor necrosis factor inhibitor (TNFi) era.
TNF-α plays an important role in AS and is the core cytokine mediating the inflammatory process of AS. A large amount of evidence-based medical evidence shows that TNFi can rapidly and effectively relieve patients' AS symptoms and reduce disease activity compared with the traditional drug therapy era.
Currently, TNFi approved for the treatment of AS include infliximab, adalimumab, Golimumab, etanercept, cetuzumab, and recombinant human tumor necrosis factor type II receptor-antibody fusion protein.
The 3.0 Era
The 3.0 era, the era of Interleukin.
IL-17 plays an important role in multiple links of the occurrence and development of AS, participating in the development of attachment site inflammation and pathological new bone formation, which can lead to irreversible structural damage.
Currently, the global approved IL-17 inhibitors for the treatment of AS include Cosentyx (secukinumab) from Novartis, Taltz (ixekizumab) from Eli Lilly and Efleira (Netakimab) from Biocad.
Several new drugs have also been approved in the AS field in recent years, such as the JAK inhibitors tofacitinib and upatinib. Both drugs are approved for use in adult patients with active AS who have an inadequate or intolerant response to one or more TNFIs. However, unlike the biologics mentioned above, tofacitinib and upatinib are both small molecules and are administered orally.
A number of new drugs have been developed to treat AS. It can be seen that the new drug targets for AS are mainly IL-17 and JAK, but MK2 and PDE4 targets have been developed for the treatment of AS.
With the continuous progress of stem cell technology, more and more experimental data show that mesenchymal stem cells are the ideal cell choice for human autoimmune disease cell therapy.
Studies have found that AS is closely related to autoimmune function. The imbalance of Th17/Treg cell subsets in the blood of patients with AS leads to immune disorders, obvious disorders of immune function and various tissue damage.
Umbilical cord mesenchymal stem cells (UC-MSCs) have strong proliferation and differentiation ability, and can surround the diseased cells deep in the lesion within a short time after transplantation. With the further proliferation and differentiation of cells in the body, the damaged cells can be repaired while the dormant cells can be activated, and their corresponding functions can be gradually restored. MSCs transplantation therapy can correct the imbalanced immune mechanism and achieve the effect of treating both symptoms and root causes.
In 2017, a study on "Clinical Efficacy of mesenchymal stem cells in the treatment of coercive spondylitis" by Dr. Peng Xiao and his team from Halison International Peace Hospital in Hengshui, Hebei Province, published in Hebei Medical Journal, showed that the use of mesenchymal stem cell therapy could effectively improve the blood routine and liver function level of patients with AS, the patients' pain was significantly relieved, and the activity index score was significantly decreased.
AS can not be cured, the recurrence frequency is high, AS is also known as "deathless cancer".
At present, the therapeutic drugs in the current AS guidelines are mainly non-steroidal anti-inflammatory drugs (NSAIDs), biological disease-modifying drugs (bDMARDs), sulfoazine, glucocorticoids, etc.
Among them, NSAIDs often appear as first-line treatment drugs, and bDMARD treatment is usually recommended for patients with inadequate response to NSAIDs, but many patients do not achieve the expected therapeutic goals in bDMARD treatment.
Moreover, overall treatment options for AS are still limited compared with RA or PsA, and more highly effective drugs are still needed.
