What is the research progress of "early rheumatoid arthritis"?

*For medical professionals to read only for reference APLAR 2021: The new ERA standard can be used in routine clinical practice
.

 The 23rd Asia Pacific Association of Rheumatology Association (APLAR) Annual Meeting was held in Kyoto, Japan from August 28 to 31, 2021.
The meeting provided a forum for the exchange of cutting-edge scientific and clinical information, and provided participants with world-class research, Scientific and medical content
.

Among them, Professor Debashish Danda, Chairman of APLAR, shared the research progress of early rheumatoid arthritis (ERA), including what is ERA, the onset time of ERA, why the early diagnosis of ERA is important, how to diagnose ERA early, and the relevant classification standards of ERA, etc.
Progress, aimed at calling for attention and vigilance to ERA
.

This article organizes the wonderful content of this topic for readers
.

The development of RA, the existing data of these six stages indicate that the current treatment strategy for rheumatoid arthritis (RA) should focus on early recognition and diagnosis, and then early initiation of disease-improving anti-rheumatic drugs (DMARDs) treatment
.

Ideally, less than 3-6 months after the onset of symptoms, ERA treatment can increase the success rate of disease remission and reduce joint damage and disability [1]
.

The definition of ERA in the speech by Professor D.
Danda, the chairperson of APLAR: The course of disease was less than 5 years.
By the early 1990s, the relevant standard had been reduced to 24 months or less-paying more attention to the course of the disease in the first 12 months
.

Definition of VeryEarly RA (very early rheumatoid arthritis): A disease with symptoms less than 12 weeks
.

The six stages of RA development: A.
Genetic susceptibility B.
Environmental factors trigger C.
Systemic autoimmunity D.
No clinical symptoms of arthritis Undifferentiated arthritis F.
RA Figure 1: Pre-development stage model of RA [1] In the RA development model, the disease may start from genetic risk and exposure to environmental risk factors (stage 1), leading to asymptomatic inflammation and autoimmunity (stage 2)
.

Over time, autoimmunity will develop into symptomatic inflammatory arthritis (stage 3) and may further develop into classifiable RA (stage 4)
.

The transition mechanism between these stages is not yet clear, but it may involve complex relationships between the host and environmental factors, which may vary from stage to stage
.

Prevention of disease progression can be implemented at several points along the path of disease development [1]
.

How to diagnose rheumatoid arthritis early? Henk Visser et al.
[2] developed a clinical model to predict the outcome of 3 forms of arthritis at the first visit: self-limiting, persistent non-erosive, and persistently erosive joints Inflammation
.

Standardized diagnostic evaluations were performed on 524 ongoing, newly referred early arthritis patients
.

The potential diagnostic determinants obtained from the patient's medical history, physical examination, blood and imaging examinations at the first visit were input into logistic regression analysis
.

The arthritis results were recorded during the 2-year follow-up
.

The results showed that the developed prediction model consisted of 7 variables: the duration of symptoms at the first visit, morning stiffness> 1 hour, arthritis> 3 joints, bilateral compression pain of the metatarsophalangeal joints, rheumatoid factor (RF ) Positive, anti-cyclic citrullinated peptide antibody (anti-CCP antibody) positive and erosion (hands/foot)
.

Applying this model to individual patients yielded 3 clinically relevant predictive values: one for self-limiting arthritis, one for persistent non-erosive arthritis, and one for persistent erosive arthritis
.

Model 1 was developed by inputting all diagnostic variables (except genotyping) into a logistic regression model
.

According to the staged diagnostic evaluation of clinical practice, the model was developed in 2 steps
.

The model consists of 7 standards
.

Model 2 is composed of 8 standards: the 7 standards of Model 1 and the DQRA homozygosity standard
.

Model 3 was obtained by including only variables with no inter-observer variability or minimal variability into the logistic continuity rate model, including standard gender (OR 1.
63), IgM-RF positive (OR 2.
91), anti-CCP (OR 5.
0) X-rays of, opponent and/or foot (OR 3.
93) and homozygous DQRA (OR 2.
14)
.

Except for the erosive criteria, all criteria have similar ORs in terms of the correlation with persistent arthritis and the correlation with persistent erosive arthritis
.

The importance of MRI in the diagnosis of early inflammatory arthritis.
Bilateral evaluation of hands and wrists in untreated early inflammatory arthritis (IA): a comparison of ultrasound and magnetic resonance imaging and found that when total joint and tendon counts are considered, Magnetic resonance imaging (MRI) is a better predictor of RA than total ultrasound (US).
In early arthritis, MRI is better than US in predicting synovitis, and MRI has a higher diagnostic ability [3]
.

Figure 2: MRI and US sensitivity and specificity comparison [3] Figure 3: US and MRI joint and tendon counts used to identify the diagnostic performance of the receiver operating curve of RA [3] the new ERA standard in the rheumatoid population Preliminary verification This is a classification standard study for ERA, the research object is early (symptom duration <1 year) IA patients
.

A total of 803 patients were enrolled.
By the end of the one-year follow-up, 514 patients were diagnosed with RA, 251 were diagnosed with other rheumatic diseases, and 38 were diagnosed with undifferentiated arthritis
.

ERA is defined as the existence of 3 or more criteria: 1) morning stiffness ≥ 30 minutes; 2) arthritis in 3 or more joint areas; 3) hand arthritis; 4) RF positive; 5) anti-CCP antibody positive [ 4]
.

Table 1: Classification standards of ERA.
The comparative study of the new ERA standard and the ACR/EULAR standard in 1987 and 2010 recruited 417 IA patients.
By the end of the 1-year follow-up, 399 patients (95.
7%) were diagnosed and 18 ( 4.
3%) patients still had undifferentiated arthritis
.

Among the confirmed patients, 202 (50.
6%) patients were diagnosed as RA, and 197 (49.
4%) patients were diagnosed as non-RA
.

Comprehensive evaluation, the sensitivity of the ERA standard is equal to the 2010 ACR/EULAR standard (both 72.
3%), but much higher than the 1987 ACR standard (72.
3% vs.
39.
1%, P＜0.
001); the specificity of the ERA standard is the same as that of 2010 The ACR/EULAR standard is equivalent (87.
8% vs.
83.
2%), and both are slightly lower than the 1987 ACR standard (87.
8% vs.
92.
4%, P<0.
001) [5]
.

2020 ERA Standard International Multi-Center Verification An international multi-center study is to evaluate the newly proposed ERA standard and compare it with the 1987 ACR and 2010 ACR/EULAR standards
.

A total of 606 patients from China, Sweden, and India who had a disease course of ≤2 years and ≥16 years of age and were diagnosed with RA or non-RA were enrolled
.

Record clinical and laboratory parameters
.

The sensitivity, specificity, predictive value, likelihood ratio (LR) and area under the ROC curve (AUC) of the three criteria in these cohorts were compared
.

The Kappa coefficient is used to calculate the agreement between the three standards
.

Figure 4: Three standard receiver operating characteristic curves in the overall population, three standard receiver operating characteristic curves in very early arthritis patients Figure 5: Three standard receiver operating characteristic curves in very early arthritis patients with a disease course of less than 3 months Sensitivity, specificity, PPV, and NPV are in line with ERA and non-RA patients.
The Venn diagram of the number of patients with three different classification criteria is compared with the 2010 ACR/EULAR standard.
The ERA standard has significantly higher specificity (83.
7%) For 78.
2%, p=0.
02) and the sensitivity is similar (79.
2% vs.
78.
5%, p=0.
883)
.

Compared with the ACR standard in 1987, the ERA standard has higher sensitivity (79.
2% vs.
54.
5%, p<0.
001) but slightly lower specificity (83.
7% vs.
89.
1%, p<0.
001).
The AUC of the ERA standard (79.
2% vs.
54.
5%, p<0.
001) 0.
878) is equivalent to the 2010 ACR/EULAR standard (0.
849) and higher than the 1987 ACR standard (0.
791, p<0.
0001)
.

Therefore, the ERA standard shows better cross-ethnic performance in the early diagnosis of RA, and it is more feasible in daily practice [6]
.

To verify the effect of ERA's early intervention on the prognosis.
It is hypothesized that intervention in the pre-CSA arthritis stage of subclinical joint inflammation can effectively prevent arthritis from becoming chronic ("chronic")
.

The current proof-of-concept study will test this hypothesis, and the ultimate goal is to reduce the disease burden of RA [7]
.

Figure 6: Schematic diagram of TREAT EARLIER test objectives.
Finally, Professor Danda summarized the above ERA content.
Diagnosing ERA and VERA is very important to improve the results; MRI/USG is an auxiliary tool for diagnosing ERA and VERA; the new ERA standard can be used in routine practice
.

References: [1]M Kristen Demoruelle et al.
Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis.
CurrRheumatol Rep.
2012 Oct;14(5):472-80.
[2]Demoruelle MK,Deane K D.
Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis[J].
Current Rheumatology Reports,2012,14(5):472-480[3]NavalhoM,Resende C,Rodrigues AM,et al.
Bilateral Evaluation of the Hand and Wrist in Untreated Early Inflammatory Arthritis:A Comparative Study of Ultrasonography and Magnetic Resonance Imaging[J].
Journal of Rheumatology,2013,40(8):1282-92.
[4]Zhao J,Su Y,Li R,et al.
Classification criteria of early rheumatoid arthritis and validation of its performance in a multi-centre cohort[J].
Clinical&Experimental Rheumatology,2014,32(5):667-673.
[5]Ye Hua et al.
Comparison of three classification criteria of rheumatoid arthritis in an inception early arthritis cohort[J].
Clinical Rheumatology,2016,35(10):2397-2401.
[6]Ru Li et al.
Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.
[J].
Clinical and experimental rheumatology,2020;38(5):841-847.
[7]NiemantsverdrietE,Dakkak YJ,Burgers LE,et al.
TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis (TREAT EARLIER): a randomized, double-blind, placebo-controlled clinical trial protocol[J].
Trials,2020,21(1).
Source of this article: Rheumatology Channel in the Medical Circle This article is organized by: Zhang Qin, editor in charge: cassette copyright statement The original text of this article is welcome to forward the circle of friends-End-Clinical and experimental rheumatology,2020;38(5):841-847.
[7]NiemantsverdrietE,Dakkak YJ,Burgers LE,et al.
TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis(TREAT EARLIER):a randomized, double-blind,placebo-controlled clinical trial protocol[J].
Trials,2020,21(1).
Source of this article: Medical Rheumatism Channel This article is organized by: Zhang Qin Responsible Editor: Cassette Copyright Statement -Clinical and experimental rheumatology,2020;38(5):841-847.
[7]NiemantsverdrietE,Dakkak YJ,Burgers LE,et al.
TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis(TREAT EARLIER):a randomized, double-blind,placebo-controlled clinical trial protocol[J].
Trials,2020,21(1).
The source of this article: Medical Rheumatism Channel This article is organized by: Zhang Qin Responsible Editor: Cassette copyright statement -