New revelation from TICOSPA research: axSpA standard treatment, is it a reality or a utopia?

*It is only for medical professionals to read for reference.
How to better achieve the treatment of axSpA? Axial spondyloarthritis (axSpA) is a chronic progressive disease.
The formulation of scientific and reasonable treatment strategies will help guide its standardized treatment
.

Standard treatment is a treatment strategy that focuses on achieving and maintaining a clear and quantifiable treatment goal (the treatment goal is usually disease remission or low disease activity), which can maximize the quality of life of patients and prevent the appearance of poor prognosis [1-2]
.

However, the application of standard treatment in the field of axSpA is full of controversy; "You sing it, I will appear on the stage", the academic community's view on standard treatment has been changing: on the one hand, standard treatment may improve the patient's physical function and overall quality of life, and bring about Better treatment outcome
.

In 2017, a report of the European Union Against Rheumatism (EULAR) recommended that ASDAS should be evaluated as the first choice in SpA-compliant treatment strategies.
In addition, imaging results, patient comorbidities and other factors should be considered [3]; on the other hand, there is still a lack of There is no absolute consensus reference for target setting that can effectively prove that the efficacy of standard treatment is significantly better than that of conventional treatment
.

The 2019 American College of Rheumatology (ACR)/American Spondylitis Association (SAA) updated guidelines pointed out that the standard treatment strategy may bring additional burdens to doctors and patients, and this strategy is not recommended until there is direct evidence [4]
.

Is axSpA standard treatment a reality or a utopia? The results of a multicenter prospective exploratory study (TICOSPA study) comparing the clinical outcomes of axSpA standard treatment and conventional treatment were recently published in Annals of the Rheumatic Diseases (IF: 16.
102) [5]
.

What enlightenment does this research bring us? TICOSPA research: up-to-standard treatment, "good quality and low price"! ▌ Study design The study included a total of 160 axSpA patients in 18 centers in Europe
.

The enrolled patients met the axSpA diagnostic criteria proposed by the International Association for the Assessment of Spondyloarthritis (ASAS), did not respond well to non-steroidal anti-inflammatory drugs (NSAIDs) and were not treated with any biological agents, and had ASDAS ≥ 2.
1 (disease activity) at the time of enrollment )
.

The patients were randomly divided into 1:1 intensive treatment (standard treatment) group (TC/T2T group) and conventional treatment group (UC group) (Figure 1).
The total study period was 1 year
.

After the end of the study, a total of 144 cases (72 cases/group) completed the collection of all follow-up visits, and evaluated all study results from the perspective of patients
.

Figure 1: The primary endpoint of the TICOSPA study design is the proportion of patients whose ASAS health index (ASAS-HI) improved by ≥30%
.

Secondary endpoints include multiple indicators such as disease activity, patient's physical and functional status, quality of life, and safety
.

▌ Research results 1.
The curative effect is relatively better, and the safety is equivalent! In the assessment of the primary endpoint, the TC/T2T group was not significantly better than the UC group
.

After adjustment, the proportion of patients with ASAS-HI improvement ≥30% in the TC/T2T group and the UC group was 47.
3% and 36.
1%, respectively (p=0.
079, Figure 2), and the difference was not statistically significant
.

Figure 2: The proportion of patients with ASAS-HI improvement ≥30% in the two groups after 1 year of follow-up.
The evaluation results of multiple secondary endpoints are obviously more inclined to the TC/T2T group
.

For example, in the assessment of disease activity ASDAS, the proportion of patients with ASDAS<2.
1 in the TC/T2T group and UC group were 76.
5% and 59.
5% (p<0.
05), respectively; while in the assessment of the ASAS 40 response rate, the two groups reached The proportion of patients with ASAS 40 was 52.
3% and 34.
7% respectively (p<0.
05)
.

The TC/T2T group has a numerical advantage in most end-point assessments (Table 1, the red-marked items are secondary end-point indicators with significant differences between the two groups)
.

Table 1: Secondary endpoint assessment (at week 48) QALY: quality-adjusted life years; ASDAS CII: clinically significant improvement in AS disease activity score; ASDAS MI: significant improvement in AS disease activity score; LDA, low disease activity; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Function Index; BASG, Bath Ankylosing Spondylitis Overall Score; EQ5D: European Five-Dimensional Health Scale The safety of the two groups is equivalent (Table 2)
.

The number of infections in the TC/T2T group and the UC group were 15 and 16 respectively, of which there were 2 severe infections in the UC group
.

Table 2: Summary of adverse events in each group during the study period 2.
Life is more beautiful and the price is lower! The prescription rate of biologics in the TC/T2T group increased significantly after the start of the study.
By the end of the follow-up, the prescription rates of biologics in the two groups were 56.
2% and 27.
2%, respectively (TC/T2T group vs.
UC group, p<0.
01)
.

During the 48-week follow-up, patients in the TC/T2T group increased the number of visits to the rheumatology department and the number of days using biological agents, while the number of days receiving physical therapy and rehabilitation care (especially days of sick leave) decreased
.

Compared with the UC group, the TC/T2T group increased by 0.
04 QALY and saved 472 Euros, indicating that the standard treatment strategy has certain economic benefits
.

▌ Analysis and discussion TICOSPA is the first study to evaluate the potential benefits of axSpA treatment
.

Among them, the TC/T2T group set a very specific goal, that is, ASDAS≤2.
1.
If the target is not met, intensive treatment will be given
.

ASDAS is a composite index reflecting disease activity, with good effectiveness, feasibility, sensitivity and high discrimination ability, and is a good index for evaluating the efficacy of axSpA [6]
.

It has a well-proven cutoff value.
Compared with ASDAS<1.
3 (defined as disease remission/inactivity), ASDAS<2.
1 (remission or low disease activity) is considered to be a more suitable treatment target, and good Symptom relief, physical function, delay in imaging progress, and improvement in quality of life are related [2-3,6-10]
.

Compared with the TICORA and TICOPA studies, which set the primary end point as an indicator of disease activity, the TICOSPA study set the primary end point as the result of disease activity—that is, the improvement of the patient’s health-related quality of life and activity function (ASAS-HI) , Which more directly reflects the outcome of different treatment strategies [5]
.

In addition, considering the slow progression rate and low prevalence of axSpA (compared to diabetes and hypertension), in order to reduce the difficulty of implementing the TC/T2T strategy, the study did not monitor the effects of different treatment strategies on preventing and delaying structural damage.
There is also not too much attention to the difference in the risk of comorbidities, which may have an important impact on the research results [5]
.

We can go further if treatment reaches the standard! The research results of TICIOSPA affirmed the benefits of axSpA standard treatment, and provided favorable support for the implementation of the clinical standard strategy
.

But how can we truly achieve axSpA treatment? Are there enough weapons and means to help us meet the standards? Therapeutic drugs have a very important position in the path to axSpA standards
.

In recent years, various innovative drugs have appeared one after another, which has enriched patients' drug choices and helped them achieve disease control faster and better and achieve deeper standards
.

Among them, the interleukin-17A (IL-17A) inhibitor is a new type of biological agent in the treatment of axSpA, and the IL-17A inhibitor skukuzumab is the first interleukin approved for the treatment of ankylosing spondylitis (AS) in China.
Inhibitor
.

Studies have shown that the proportion of patients who have achieved disease remission or low disease activity as defined by ASDAS is high after Skuchiyuumab treatment.
It can effectively control disease symptoms and inhibit the progress of imaging, helping to achieve standard treatment[11-13]
.

Currently, a comparative study (AScalate, NCT03906136) is underway to explore the effectiveness of a standard treatment strategy with Skuchiyuumab as a first-line biological agent for the treatment of active axSpA (AScalate, NCT03906136).
This multi-center phase III clinical trial is underway.
The study is expected to be completed in June 2022, and it is hoped that the results of the study will give us more confidence in T2T treatment strategies
.

Figure 3: The ongoing AScalate research.
In addition, with the development of imaging technology [15-20], the discovery of new biological markers [21-22], the development of modern auxiliary tools and the application of big data [23- 25], the early diagnosis of disease and patient management have more diversified paths
.

Flexible use of existing treatment management strategies and modern technology will help us to go further and further on the road to achieving standards, and the future can be expected! Reference materials: [1] Pedro M Machado et al.
Curr Opin Rheumatol.
2019 Jul;31(4):344-348.
[2] Xu Shengqian, Huang Feng.
Chinese Journal of Internal Medicine, 2019,58(10):705-708 .
[3]Smolen JS,et al.
Ann Rheum Dis.
2018 Jan;77(1):3-17.
[4]Ward MM,et al.
Arthritis Care Res(Hoboken).
2019 Oct;71(10): 1285-1299.
[5]Molto A,et al.
Ann Rheum Dis.
2021.
doi:annrheumdis-2020-219585.
[6]Machado PM,et al.
Best Pract Res Clin Rheumatol.
2014 Oct;28(5): 711-28.
[7]C Popescu,et al.
J Med Life.
2014 Mar 15;7(1):78-83.
[8]van Lunteren et al,Rheumatology 2017:56:2222-8.
[9] van der Heijde D et al.
J Rheumatol 2014;41:1095–1103.
[10]Franco Gomez K,Arthritis Rheumatol.
2020,72(suppl 10).
Abstract Number 0893.
[11]Baraliakos X,et al.
Annual European Congress of Rheumatology(EULAR),June 12-15,2019,Madrid,Spain.
,#FRI0386.
[12]Baraliakos X,et al.
Ann Rheum Dis.
2015;74281.
[13]Braun J et al.
Rheumatology(Oxford ).
2019;58(5):
.

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