For these patients at high risk of AS structural damage, the long-term benefits of treatment are the key!

*Only for medical professionals to read for reference.
A number of studies have explored the predictive factors of long-term structural damage in AS, which may bring new inspiration for clinical treatment.

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease characterized by inflammatory low back pain, which can seriously affect the life of patients and bring a heavy burden to patients.

In 2019, the results of a real-world study of 820 patients with AS in the United States showed that AS had a significant negative impact on patients' activity ability, work ability, career choice and life [1].

Systematic literature reviews and other research reports also pointed out that AS patients have low employment rates, long absences from work, and high employment barriers.
The decline in productivity caused by AS disease itself accounts for the highest proportion of disease costs [2].

In clinical treatment, in addition to pain, morning stiffness and other clinical symptoms and signs that need to be paid attention to, the impact of long-term structural damage should also not be ignored.

Studies have shown that the quality of life of patients with AS is significantly negatively correlated with structural damage, and patients with a longer course of disease have more severe structural damage [3].

At the same time, the spinal structure damage of AS patients is like a "warm water boiled frog", the slow period is not easy to be detected, but rapid progress can occur in the later stage [4], and the physical disability caused by structural damage is irreversible [5].

Therefore, authoritative guidelines at home and abroad unanimously point out that: control of symptoms and prevention of structural damage are the treatment goals of AS [6-9].

Early intervention measures to delay the progression of the patient's disease and protect the joint structure are the key links and important goals of AS treatment, and are closely related to the improvement of patients' mobility and the improvement of long-term quality of life.

Figure 1 Controlling symptoms and preventing structural damage are both the treatment goals of AS[6-9]1 What factors can predict AS structural damage? Before and during the treatment of AS, it is very meaningful if some means can be used to predict structural damage, so as to judge whether the patient's condition will develop rapidly and predict the long-term treatment effect.

In a review published in Joint Bone Spine in 2020, researchers summarized relevant studies in recent years and pointed out [10]: Over time, high disease activity is significantly associated with spinal structural damage.

Some biomarkers, such as C-reactive protein (CRP), matrix metalloproteinases (MMP-3), vascular endothelial growth factor (VEGF), calcium binding protein, visfatin, etc.
are related to AS structural damage, but currently only CRP An indicator is recommended for clinical practice as a predictor of structural damage in AS patients in traditional therapy and tumor necrosis factor inhibitor (TNFi) therapy.

The presence of osteophytes at baseline is a strong predictor of structural damage, but now the main purpose is to predict structural damage before the first osteophyte is formed.

The presence of inflammation and fat on MRI has become a strong predictor of new osteophytes.

Among the commonly used clinical evaluation tools, ASDAS-CRP can independently predict the structural damage of patients with early axial spondyloarthritis (axSpA) after 2 years (mSASSS progression ≥ 2 and ligament osteophyte progression/formation).

Whether gender is related to structural damage still needs further exploration.

Smoking has a certain correlation with structural damage in male AS patients.

Whether the patient is male or female, obesity is a predictor of long-term structural damage in AS patients.

At the 2020 EULAR meeting, a number of related studies have successively released the results to further explore the predictive factors of AS structural damage.

A cross-sectional study included 112 patients with SpA.
The results showed that the BASRI lumbar index (BASRI-L) and BASRI spine index (BASRI-S) of male patients were significantly higher than those of females.
The modified Stoke ankylosing spondylitis spine index of smoking patients (MSASSS), BASRI Cervical Spine Index (BASRI-C) and BASRI-S Index were significantly higher than non-smokers (Figure 2).

In addition, studies have shown that the duration of the disease is significantly positively correlated with BASRI-C and BASRI-S.

Research suggests that men, smoking, and duration of disease are related to AS spinal structure damage (Figure 2) [11].

Figure 2 Men, smoking and spinal structure damage are related to a Swiss prospective cohort study that included 88 radiology-negative axSpA (nr-axSpA) and 418 radiology-positive axSpA (r-axSpA) patients.

The results showed that the mSASSS score changes of patients with r-axSpA were significantly higher than that of nr-axSpA (Figure 3).

In addition, whether patients with nr-axSpA or r-axSpA, baseline ligament osteophytes can be used as a predictor of the progression of mSASSS [12].

Figure 3 The change of mSASSS in patients with r-axSpA was significantly higher than that in patients with nr-axSpA, which is a common symptom of AS.

A retrospective cross-sectional study included 112 patients with SpA.
Multivariate analysis showed that sacroiliac arthritis was more common in patients with hip joint involvement, and the mSASSS score was significantly higher in patients with hip joint involvement (Figure 4), suggesting hip joint involvement Or it is related to spinal structure damage [13].

Figure 4 The mSASSS score of AS patients with hip joint involvement is significantly higher than that of patients without hip joint involvement.
2 Delaying the structural damage of AS patients, the prospects of skukuzumab are promising, and the clinical treatment of AS is still limited.

And many studies have shown that conventional anti-rheumatic drugs (csDMARDs), TNFi and other drugs to treat AS cannot help patients delay structural damage.

In the treatment of AS, csDMARDs are usually recommended only in patients with peripheral arthritis.

A follow-up study of 301 AS patients who received csDMARDs treatment showed that csDMARDs treatment did not show a significant effect in delaying AS spinal structure damage [14].

A meta-analysis of a total of 3186 AS patients included in 14 studies showed that compared with the group of patients who did not receive TNFi treatment, patients who received TNFi treatment for 2 years and more than 2 years had no significant difference in mSASSS scores, suggesting TNFi treatment The mSASSS score is not improved, and the radiological progress of AS patients cannot be inhibited [15].

Interleukin-17A (IL-17A) inhibitor Recchiumab has shown a relatively good effect in delaying the radiological progress of AS.

A small sample study showed that 87% of vertebral marginal inflammation disappeared in patients with AS with Skuchiyuumab for 94 weeks, 70% of vertebral marginal fatty lesions did not progress, and 30% of vertebral marginal fatty lesions disappeared [16].

The MEASURE 1 study showed that when AS patients were treated with Skuchiyuumab for 104 weeks, 97% of patients without osteophytes at baseline (n=53) did not develop new osteophytes; in patients with osteophytes at baseline (n =51), 73% did not produce new osteophytes (Figure 5) [17].

Figure 5 Proportion of patients with and without osteophytes at baseline and no new osteophytes after receiving Skucilumab treatment.
After 208 weeks of treatment, nearly 80% of patients had no radiological progression (mSASSS change from baseline to week 208< 2) (Figure 6) [18].

Studies have confirmed that the long-term treatment of AS patients with Skuchiyuumab can delay the progress of radiology and inhibit the formation of new bone.

Figure 6 Skucilumab can delay the radiological progress of AS patients.
3 Summary The long-term structural damage of AS has a serious impact on the life of patients.
In clinical practice, doctors should pay attention to the long-term improvement of the drug while paying attention to the improvement of symptoms in AS patients.
Period efficacy.

A number of studies have explored the predictive factors of long-term structural damage in AS, which may bring new inspiration for clinical treatment.

Among the currently commonly used drugs in clinical practice, the long-term application of Skucilizumab can effectively delay the radiological progress of AS and bring more long-term benefits to patients.

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The MCC number CXA2104610 is valid for 2022-04-09, and the data is expired and deemed invalid. A review of the changes in the treatment of ankylosing spondylitis in the past: from "symptomatic treatment" to "total management", the new medical insurance catalogue is officially implemented.
What changes will it bring to the diagnosis and treatment of AS? The latest medical insurance drug list is implemented, IL-17A inhibitors will benefit more rigid patients! "Inflammation" must be lost, and anti-inflammatory methods: The relationship between IL-17A and inflammation is explored.
What is the relationship between IL-17A and the pain of ankylosing spondylitis? What changes will the introduction of IL-17A inhibitors into medical insurance bring to the AS "ecological circle"?