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Is it difficult to achieve standard treatment for AS? The new standard may be useful!

 Last Update: 2023-01-01
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*For medical professionals only, there is no perfect evidence for T2T, further research and improvement

is neededThe 2022 American College of Rheumatology Annual Meeting (ACR) was held on November 10~14,

The big names in the field of rheumatology and immunity gathered to bring you the latest research results
.
Alexis from the University of Pennsylvania Professor Ogdie discussed "Standard treatment of ankylosing spondylitis
".

The "medical community" and the experts of the Youth Committee of the Rheumatology Branch of the Chinese Medical Association quickly, comprehensively and deeply brought the live interpretation of ACR 2022, hoping to connect with the international cutting-edge information and combine with Chinese clinical practice
with colleagues in the Department of Rheumatology and Immunology.

In this issue, Professor Zheng Zhaohui of the First Affiliated Hospital of Air Force Military Medical University gave a wonderful interpretation
of the standard treatment of ankylosing spondylitis.

In
recent years, Treat to Target (T2T) has been used in the management of many chronic diseases, such as hypertension and diabetes, and its important clinical outcomes have been well improved
.
Rheumatic diseases such as gout, rheumatoid arthritis and psoriatic arthritis have also introduced the concept
of T2T.
Many experts and scholars also advocate the inclusion
of T2T in axial spondyloarthritis (axSpA).
So how do rheumatologists practice medicine for ankylosing spondylitis at present?
Professor Zheng Zhaohui introduced that for patients with ankylosing spondylitis, it is common practice to first evaluate their symptoms and signs, and the current Ankylosing Spondylitis Disease Activity Index (BASDAI) is the most widely used disease activity assessment index
in axSpA.
There are six questions, all answered by the patient for the condition of the past week:
overall degree of fatigue/sleepiness;
overall degree of neck, back, and hip pain;
the overall degree of pain/swelling in other joints (excluding neck, back, hip);
the overall degree of discomfort due to tenderness or tenderness;
severity of morning stiffness after waking up;
Duration of morning stiffness after waking
.

Since then, relevant examinations have been improved, including CRP, HLA-B27, sacroiliac joint X-ray examination, sacrum MRI, etc
.
After diagnosis, non-drug and drug combination and combination treatment
are carried out according to existing recommendations.
Non-drug treatments include: functional exercise, physical therapy, etc.
, drug treatments include: nonsteroidal anti-inflammatory drugs (NSAIDs), biologics anti-rheumatic drugs (bDMARDs), targeted synthetic DMARDs (tsDMARDs), etc
.

Figure 1 Treatment toolbox for ankylosing spondylitis

However, there are many problems
with this treatment option at present.
Whether radiologically positive axSpA (r-axSpA) or radiographically negative axSpA (nr-axSpA) patients, this treatment regimen still does not achieve good results, and studies have shown that only about half of patients achieve ASAS40 response ^[1].
In addition, patients have residual symptoms such as pain and fatigue after treatment ^[2].

What does "mark" mean, and where does the sword point?

The 2016 International Association for the Evaluation of Spondyloarthritis (ASAS) and the European Union Against Rheumatism (EULAR) updated management guidelines support the use of T2T regimens in axSpA
。
T2T is a completely new treatment concept and management model, from disease activity status criteria to response criteria, axSpA compliance treatment goals have changed several times
.
However, due to the bias of doctors and patients' cognition of different achievement indicators and the lack of relevant data, there are certain difficulties
in setting targets in SpA's T2T.
With axSpA, the main goal of T2T is to delay disease progression and prevent joint destruction
.
At present, although there are many axSpA evaluation indicators, some indicators are not sensitive and specific, or difficult to detect and achieve
in actual clinical work.
At present, it is widely accepted as the main criterion for achieving the criteria for axSpA patients as AS disease activity score (ASDAS
).

Studies have shown that ASDAS can distinguish the efficacy of treatment group and placebo group well among different efficacy indicators of axSpA, has good resolution, and can respond sensitively and effectively to the patient's disease state ^[3].

ASDAS has well-validated cut-off values: ASDAS <1.
3, 1.
3< ASDAS <2.
1, 2.
1< ASDAS <3.
5, ASDAS >3.
5 correspond to disease remission, low disease activity, high disease activity, and very high disease activity
, respectively.

In the SpA recommended treatment strategy updated by the International Working Group in 2017, the target treatment strategy with ASDAS score as the evaluation criterion was clarified ^[4].

Figure 2 ASDAS-CRP scoring criteria

However, is there a problem with the development of this target in axSpA practice?
Unsatisfactory – clinical practice of T2T

1.
Lack of evidence-based medical evidence

Figure 3 TICOSPA findings

The TICOSPA study is a one-year international multicenter study ^[5] that explores differences
in various aspects of intensive and conventional treatment (UC).
In the trial, patients with axSpA with ASDAS>2.
1 were randomly assigned to TC and UC groups: in the TC group, a treatment strategy was pre-developed based on scientific advice with the goal of keeping the patient's ASDAS below 2.
1; in the UC group, the rheumatologist could decide the treatment regimen
at his or her discretion.

The results showed that the proportion of patients with 30% improvement in ASAS-HI ≥ the primary outcome of the TC and UC groups was 47% and 36%, respectively, with no significant differences; In the assessment of disease activity, the proportion of patients in the TC group and UC group achieving ASDAS <2.
1 was 77% and 60% (p<0.
05), respectively, and the response rate of ASAS40 was 52% and 35% (p<0.
05),
respectively.
The T2T concept in axSpA requires more clinical evidence that it is superior to current clinical conventional care
.

2.
A variety of factors affect the treatment effect

Studies have shown that depression affects patients' response
to treatment.
For non-depressed patients, BASDAI, ASDAS, BASFI, ASQoL scores, pain and exhaustion after treatment were significantly reduced and maintained at low levels, but for patients with mild, moderate to severe depression, the treatment effect was not obvious
.
In addition to depression, hypertension, obesity, diabetes, etc.
can all affect how patients feel and thus affect their response
to treatment.
Studies have shown a significant relationship
between the number of comorbidities and the effect of axSpA treatment.

Figure 4 Depression affects patient response

Exploring new standards

in T2T Due to the unsatisfactory practice of axSpA and evidence-based medicine, the setting of treatment goals in T2T is still being actively explored
.

X-ray examination, MRI, quality of life score Professor Zheng Zhaohui mentioned several candidates in the current axSpA standard treatment - X-ray examination, MRI, quality of life score

。 X-ray is a very important tool in the diagnostic process, can it be used as a standard for T2T? Many patients with axSpA do not progress in radiology over a 10-year period, so radiology is difficult to use as a standard
for T2T due to its slow change.

MRI provides a good help in diagnosis, making the diagnosis time much earlier
.
However, studies have shown that MRI findings
can also be seen in some patients with axSpA in healthy people.
In addition, radiologists' reading standards are uneven, and there may be problems with over- or undertreatment, so MRI as a standard is limited
.

The quality of life score can directly reflect the feelings of patients after treatment, but there are many factors that affect the quality of life score, such as work, family, socialization, sleep, etc.
, which are not much related to the disease, so the quality of life score is difficult to use as a standard for evaluating the achievement of
the disease.

Profmis Score
Professor Zhaohui Zheng said that the daily life of axSpA patients may be troubled in many ways: such as fatigue (53%-76%), poor sleep (restless legs syndrome, obstructive sleep apnea), which can affect basic activities (eating, washing, wearing, Social activities), and even 10.
5%-32% of people with ankylosing spondylitis give up work or lose the ability to
work.
Therefore, axSpA treatment needs to ensure health-related quality of life and normalization
of function.

Professor Zhaohui Cheng mentioned the concept of
whole-patient care.
For patients with axSpA, not only ankylosing spondylitis should be treated, but also all aspects of the patient, such as work, family, mood, treatment cost, etc
.

The Promis-29 scale includes 7 modules (depression, anxiety, physiological functioning, pain disturbances, fatigue, sleep disturbances, social participation).

The Promis score is derived directly from a patient's report of their health, functional status, and treatment feelings, and in clinical studies, it can be used to determine treatment options and as a tool
for evaluating efficacy by measuring a patient's attitude towards their disease and the impact on daily life.

For axSpA patients, in addition to ASDAS assessment, PROMIS assessment can provide a more comprehensive understanding of the patient's status (such as depression, poor physical fitness), so as to carry out more comprehensive care treatment (mental health care, physical function treatment), which can more effectively improve the patient's quality of life
.

Figure 5 Improvement in standard treatment

summary

In recent years, due to the popularity of T2T in rheumatoid arthritis and other fields, many experts and scholars have also advocated the inclusion of the concept
of T2T in axSpA.

In ACR 2022, ankylosing spondylitis T2T once again became the focus, focusing on the current treatment process of ankylosing spondylitis, the current standards of T2T, evidence-based medical evidence and existing problems, and the exploration
of new standards.
Professor Zheng Zhaohui helped us connect with the international community, listen to cutting-edge voices, and pointed out that there is no perfect evidence for T2T in ankylosing spondylitis, and it needs to be further studied and improved, and more factors are added to the goal of T2T to better improve the prognosis
of patients.

Expert profiles

Professor Zhaohui Zheng

• Director of the Department of Clinical Immunology, First Affiliated Hospital of the Air Force Military Medical University

• Associate Chief Physician, Associate Professor, MD

• Member of the Youth Committee of the Rheumatology Branch of the Chinese Medical Association

• Vice Chairman of the Youth Committee of Shaanxi Rheumatology Branch

• Member of the Standing Committee/Director General of the Rheumatology and Immunology Branch of Shaanxi Medical Doctor Association

• Published 28 SCI papers as first author or corresponding author, and 12 editor-in-chief/associate editor/co-editor
/co-editor.
He wrote and completed 2 national expert consensuses, and led the completion of 1 expert consensus and path in Shaanxi Province
.
Won 1 first prize of Shaanxi Province Science and Technology Progress Award and 2 national utility model patents; He has presided over 10 projects such as the National Natural Science Foundation of China and the Key R&D Program of Shaanxi Province
.

References:

[1]Danve, Abhijeet, and Atul Deodhar.
“Treatment of axial spondyloarthritis: an update.
” Nature reviews.
Rheumatology vol.
18,4 (2022): 205-216.
doi:10.
1038/s41584-022-00761-z

[2] Magrey, Marina N, and Philip J Mease.
“Pain in Axial Spondyloarthritis: More to It Than Just Inflammation.
” The Journal of rheumatology vol.
48,11 (2021): 1632-1634.
doi:10.
3899/jrheum.
210137

[3]A.
Ortolan, et al.
Ann Rheum Dis, volume 79, supplement 1, year 2020, page 194.

[4] Smolen JS, et al.
Ann Rheum Dis.
2018 Jan; 77(1):3-17.

[5] Molto, Anna et al.
“Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.
” Annals of the rheumatic diseases vol.
80,11 (2021): 1436-1444.
doi:10.
1136/annrheumdis-2020-219585

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