Why did the structural progress of axSpA trigger heated discussions?

*For medical professionals' reference only, what new discoveries have we made for predicting and delaying the progress of axSpA structure? Let's review the exciting content related to EULAR 2021! Axial spondyloarthritis (axSpA) is a chronic inflammatory disease mainly involving the axial bones (including the sacroiliac joints and spine)
.

Although it starts with inflammation, it does not end with inflammation
.

In the progress of axSpA, irreversible structural damage may lead to physical disability and increase the burden of disease
.

How to effectively prevent and delay the progress of axSpA structure is the direction that we need to continuously explore and optimize in the treatment
.

With the unremitting efforts of scholars and experts in many fields, our understanding of axSpA disease is getting deeper and deeper, and the mystery of its structural progress is being revealed step by step
.

In this year's European Union Against Rheumatism (EULAR) annual meeting, many of the latest research developments related to this were unveiled, which triggered in-depth thinking and discussions among many experts
.

Although the conference has ended, it is wonderful not to be missed.
In this issue, we will sort out the hot topics related to the progress of bone structure in the conference, and let's review it together! Pay attention to these risk factors! TAs are a high-risk factor for structural damage! Although not all patients with axSpA will experience structural and functional damage, we should not take it lightly [1]
.

According to the disease spectrum, axSpA can be further divided into radiology negative axSpA (nr-axSpA) and radiology positive axSpA (r-axSpA).
r-axSpA is also called ankylosing spondylitis (AS) [2-3]
.

According to relevant literature reports, during a follow-up of 2-10 years, about 12%-59% of nr-axSpA patients will progress to radiologically positive AS, with irreversible structural damage, resulting in restricted mobility and dysfunction—this is not It is a small probability event that needs our attention [4-5]
.

So, the question is, can we use some predictive methods to judge the likelihood of structural damage in patients? Up to now, many studies have analyzed and explored the predictive factors of axSpA imaging progress [1]
.

The study found that patient characteristics (such as smoking, obesity, etc.
), disease activity, biomarkers [C-reactive protein (CRP)], and baseline imaging findings (such as the formation of osteophytes at baseline, or MRI showed inflammatory changes in the attachment points) Subsequent fat deposition) are highly correlated with the progression of imaging in the course of the disease (Table 1).
The presence of these high-risk factors suggests that the patient's condition may progress rapidly, leading to bone structural damage, and early interventional treatment is required
.

Table 1: Predictors of axSpA imaging progress ESR: erythrocyte sedimentation rate, also known as erythrocyte sedimentation rate; MMP-3: matrix metalloproteinase-3; VEGF: vascular endothelial growth factor; ASDAS: ankylosing spondylitis disease activity score; BASDAI: rigidity Spondylitis disease activity index; MRI-BME: The bone marrow edema (inflammatory changes) shown in magnetic resonance imaging is ideally plump, but the reality is too skinny—it is imperative to delay structural progress, but there is a long way to go.
Tumor formation is an important indicator of the progress of axSpA/AS, but osteophyte formation has caused the destruction of bone structure [6], and once the structural damage occurs, it is difficult to reverse, so early diagnosis and treatment are particularly important
.

In fact, there is a "window of opportunity" for the treatment of structural progress in axSpA patients, that is, active intervention in the early inflammatory phase to prevent structural damage to the greatest extent and improve the patient's prognosis and quality of life [6]
.

However, what is the reality of clinical diagnosis and treatment? Small domestic studies have shown that over 60% of AS patients have developed fatty deposits or osteophytes (Figure 1) [7-8], and foreign studies have similar results (Table 2) [9-18]
.

This shows that in actual clinical diagnosis and treatment, a considerable proportion of axSpA/AS patients are at risk of structural damage and further aggravation
.

Figure 1: Domestic studies have shown that a considerable proportion of AS patients have structural damage and the risk of further aggravation.
Table 2: Multiple studies have found that patients with AS or axSpA have a higher proportion of fatty lesions and ligament osteophytes at baseline [10-19] Structural damage is the main reason for the poor prognosis of patients with axSpA/AS, and it is imperative to delay the structural progress
.

Early inhibition of inflammation and inhibition of new bone formation are effective ways to prevent the progress of imaging
.

However, as the first-line treatment of AS, the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in delaying structural progress is still controversial [19-20].
The results of meta-analysis in 2020 suggest that NSAIDs may not inhibit the structural progress of AS.
[21]
.

Can biological agents bring light to the prevention of bone structure destruction in patients with axSpA? Tumor necrosis factor-α (TNF-α) inhibitor is currently a biological agent widely used in the field of AS biotherapy
.

A number of previous studies have shown that the efficacy of TNF-α inhibitors in delaying structural progress is not satisfactory: under continuous treatment, although the inflammation is well controlled, the fat deposits still increase significantly in the course of the disease[22-25]
.

The latest research released by EULAR and the American College of Rheumatology (ACR) in the past two years has shown that TNF-α inhibitors have a "delayed effect" on the delay of imaging progress, and the effect will be obvious after 2-4 years after the start of treatment.
The treatment effect is significant for more than 4 years (Figure 2) [26-27]
.

Figure 2: TNF-α inhibitors in the treatment of AS have a "delayed effect" in delaying the progress of imaging.
So, is there a way to inhibit the progress of imaging faster and better? "Aiming at" the core mechanism, which is expected to go further on the road of delaying structural progress.
New bone formation is a characteristic manifestation of AS and one of the pathological basis for its structural progress
.

The appearance of pathological new bone formation may cause osseous fusion and rigidity of the joint, which is the main reason for the patient's dysfunction
.

The formation of new bone is closely related to inflammation and lipopathy, and the coexistence of the two will greatly promote the formation of new bone and promote the progress of imaging[28-30]
.

Interleukin-17A (IL-17A) mechanism of action and targeted therapy are currently hot research directions in the AS field
.

It plays an important role in the pathogenesis of AS, especially in the process of new bone formation and participates in the regulation of bone metabolism
.

In this year's EULAR annual meeting, some researchers reported that patients with r-axSpA (AS) treated with IL-17A inhibitors for 2 years did not show significant imaging progress, and the overall average level of progress was low [31]
.

This shows that targeted inhibition of IL-17A can effectively delay the progression of AS structure
.

Skukuzumab is the first and only IL-17A inhibitor approved for the treatment of AS in China
.

The results of multiple studies have shown that scocilizumab has the effect of delaying the progression of AS imaging: alleviating inflammation of the vertebral body and reducing fat deposits-an observational study has shown that scocilizumab is effective after 94 weeks of treatment Reduce inflammation damage and fat deposition at the edge of the vertebral body in patients with AS (Figure 3) [31]
.

Figure 3: 94 weeks of Skuchiyuumab treatment, effectively reducing the inflammation and damage of the vertebral body in AS patients and reducing the formation of new osteophytes.
The MEASURE 1 study enrolled 371 patients, of which 249 patients received Skuchiyudan Anti-treatment, 122 cases in the placebo group
.

＞80% of patients in the Skuchiyuumab group did not develop new osteophytes for 2 years of treatment
.

Among them, 97% of patients without osteophytes at baseline and 73% of patients with osteophytes in ligaments at baseline did not develop new osteophytes during the 2-year treatment period (Figure 4) [10]
.

Figure 4: The MEASURE1 study showed that Skuchyumab treatment can reduce the formation of new osteophytes.
In addition, studies have conducted a horizontal comparative analysis of the effects of various biological agents on the structural progression of AS patients after 2 years of treatment [13,33]
.

The results showed that the Stoke's ankylosing spondylitis spine score (mSASSS) had the lowest mean change in the skukuzumab group (Figure 5), which means that it has a good effect in delaying the progress of imaging
.

Figure 5: A horizontal comparison of the delaying effects of various biological agents on the imaging progress of AS patients: For axSpA patients, delaying structural progress is an important means to improve their quality of life and prognosis
.

A number of studies have explored the predictive factors/high-risk factors related to the structural progress of axSpA, and the results are expected to guide clinical treatment in the future
.

In addition, IL-17A inhibitors bring hope for us to achieve the therapeutic goal of delaying structural progress.
More research and evidence-based evidence are still accumulating, or the structural progress of axSpA may be revealed, so stay tuned! Experts commented that every EULAR annual meeting will have a lot of inspiring news, especially in recent years, the understanding of SpA or AS has become deeper and deeper, and some new targeted therapies have also brought gratifying results
.

The difficulty of axSpA treatment is that there is very large heterogeneity between patients, the prognosis is relatively large, and the disease process involves the formation of compensatory osteophytes, and there is no direct treatment for the latter
.

Some new targeting methods are expected to solve these problems
.

However, due to the heterogeneity between patients, there is currently no drug suitable for all patients
.

However, doctors have been able to make a general judgment on the future development trend based on the characteristics of the patients, and can adopt more effective treatments for patients who may develop faster and have a poor prognosis
.

Early active control of inflammation is still the most meaningful method at present, do not wait until osteophytes have formed or the joint has been fused before starting treatment
.

NSAIDs, TNFi, IL-17 and IL-23 inhibitors are currently relatively mature treatments
.

In particular, IL-17A has a more prominent role in the evolution of new bone formation-inflammation-fat.
Targeted inhibition of IL-17A shows very great therapeutic potential
.

Skukuzumab is the first and only IL-17A inhibitor approved for the treatment of AS in China.
A number of studies have shown that it can alleviate the inflammation of the pyramidal edge, reduce fat deposition, and reduce the incidence of new osteophytes.
Formed
.

In particular, Skucilizumab quickly entered the social medical insurance list after its listing in China, and was used as an outpatient reimbursement drug for the treatment of AS, so that more patients can afford the price, and the use of effective drugs will surely benefit More SpA patients
.

 Expert profile Professor Gao Guanmin, deputy director of the Department of Rheumatology and Immunology, head of the Department of Rheumatology and Immunology, He Hospital District, Doctor of Medicine, Chief Physician, Professor, and Master's Supervisor Chinese Rheumatology Society National Young and Middle-aged Member of the Henan Medical Association Osteoporosis and Bone Mineral Salt Society Standing Committee Member He is also the head of the bone immunology group, deputy director of the Rheumatology Branch of the Henan Medical Science Society, deputy director of the Henan Association of Integrated Traditional Chinese and Western Medicine and Rheumatology, deputy director of the Osteoporosis Branch of the Chinese Geriatrics Association, from April 2019 to June 2020.
New York University Rheumatology Center Visits the UpToDate clinical consultant of Wolters Kluwer, a well-known publishing group, China Knowledge Network Clinical Therapy Knowledge Base Rheumatology Section Editor Expert Reference: [1]Aouad K,et al.
Joint Bone Spine.
2020 Mar;87( 2):131-136.
[2]Rudwaleit M et al.
Ann Rheum Dis.
2009:68(6):777-783.
[3]Garg N et al.
Best Pract Res Clin Rheumatol.
2014;28(5) :663-672.
[4]J Braun,et al.
Ann Rheum Dis.
2011 Mar;70 Suppl 1:i97-103.
[5]Sampaio-Barros PD,et al.
Clin Rheumatol.
2001;20(3): 201-6.
[6]Baraliakos X,et al.
Ann Rheum Dis.
2019 Sep;78(9):1220-1225.
[7].
Magnetic resonance imaging and immunopathological study of sacroiliac joint in early ankylosing spondylitis .
Doctoral Dissertation of Shantou University School of Medicine.
2015[8]Tu Liudan, et al.
Journal of Sun Yat-sen University (Medical Science Edition).
2015,36(1):24-27.
[9]Park JW,et al.
PLoS One .
2016 Dec 29;11(12):e0168958.
[10]Braun J,et al.
Ann Rheum Dis.
2017 Jun;76(6):1070-1077.
[11]Maas F,et al.
PLoS One.
2017 Jun 22;12(6):e0177231.
[12]Maas F,et al.
Arthritis Care Res(Hoboken).
2017 Jul;69(7):1011-1019.
[13]van der Heijde D,et al.
Ann Rheum Dis.
2018 May;77(5):699-705.
[ 14]Molnar C,et al.
Ann Rheum Dis.
2018 Jan;77(1):63-69.
[15]Braun J,et al.
Rheumatology(Oxford).
2019 May 1;58(5):859-868 .
[16]Pedersen SJ,et al.
Scand J Rheumatol.
2019 May;48(3):185-197.
[17]Park JW,et al.
Arthritis Rheumatol.
2019 Jan;71(1):82-90.
[18]Beek KJ,et al.
J Bone Miner Res.
2019 Jun;34(6):1041-1048.
[19]Wanders A,et al.
Arthritis Rheum.
2005,52(6):1756-65.
[ 20]Sieper J,et al.
Ann Rheum Dis.
2016,75(8):1438-43.
[21]Karmacharya P,et al.
Arthritis Rheumatol.
2020,72(5):733-749.
[22]Song IH,et al.
Semin Arthritis Rheum.
2016 Feb;45(4):404-10.
[23]Hu Z,et al.
Int J Rheum Dis.
2012 Aug;15(4):358-65.
[24] Poddubnyy D,et al.
Arthritis Rheumatol.
2016 Aug;68(8):1899-903.
[25]Konsta M,et al.
Joint Bone Spine.
2021 May;88(3):105111.
[26]Poddubnyy D, et al.
Arthritis Rheumatol.
2020,72(suppl 10).
Abstract number:1370.
[27]M.
Torgutalp,et al.
2021 EULAR Congress.
Abstract number:OP0137.
[28]Bennett AN,et al.
Arthritis Rheum.
2008 Nov; 58(11):3413-8.
[29]Buchbender C,et al.
J Rheumatol.
2015 Sep;42(9):1631-7.
[30]Baraliakos X,et al.
Ann Rheum Dis.
2014 Oct;73 (10):1819-25.
[31]D.
Van der Heijde,et al.
2021 EULAR Congress.
Abstract number:POS0918.
[32]Baraliakos X,et al.
Ann Rheum Dis.
2016 Feb;75(2): 408-12.
[33]van der Heijde D,et al.
Rheumatology(Oxford).
2019 Mar 1;58(3):388-400.
This article is only used to provide scientific information to medical and health professionals and does not represent a platform position2021 EULAR Congress.
Abstract number:POS0918.
[32]Baraliakos X,et al.
Ann Rheum Dis.
2016 Feb;75(2):408-12.
[33]van der Heijde D,et al.
Rheumatology(Oxford).
2019 Mar 1;58(3):388-400.
This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position2021 EULAR Congress.
Abstract number:POS0918.
[32]Baraliakos X,et al.
Ann Rheum Dis.
2016 Feb;75(2):408-12.
[33]van der Heijde D,et al.
Rheumatology(Oxford).
2019 Mar 1;58(3):388-400.
This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position
.