Regarding treatment options for RA biologics, what do these real-world studies show?

*Only for medical professionals to read for reference.
From another perspective, look at the performance of Abatacept in the treatment of RA
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 There are many biological agents with different mechanisms in the treatment of rheumatoid arthritis (RA), such as tumor necrosis factor-α (TNF-α) inhibitors, interleukin-6 (IL-6), IL-1 receptor antagonists And biological agents targeting B cells
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The application of biological agents with different mechanisms has made RA treatment methods increasingly diversified, enriching patients' treatment options
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Abatacept is a new type of biological agent for the treatment of RA.
It has a new mechanism of action that can regulate T cell costimulatory signals, thereby inhibiting T cell activation, indirectly inhibiting B cell activation and reducing downstream inflammation
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A number of randomized controlled trials (RCTs) at home and abroad have shown that abatacept can effectively control the condition of RA with good safety
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RCT is known for its rigorous design, and it is outstanding in terms of scientificity, standardization and rigor.
However, in clinical practice, the patient's situation is more complicated, and the extrapolation of RCT results is subject to certain restrictions
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As a good supplement to RCT, real-world research can bridge the distance between RCT and clinical practice to a certain extent, and is closer to the real clinical scenario
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So, how does Abatacept perform in real-world research? Let's look down
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In the real world, the effect is undiminished! Efficacy is the "gold standard" for testing the effectiveness of drugs, and the significant efficacy of abatacept in the treatment of RA has been further verified in multiple real-world studies
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The results of a single-center retrospective cohort study in Colombia showed that abatacept treatment can effectively reduce the activity of RA and significantly improve the disease
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After 6 months of treatment with abatacept, the disease activity index (DAS28-CRP) of RA patients decreased from 5.
0 (IQR 2) in the baseline period to 3.
4 (IQR 2); after 12 months of treatment, DAS28-CRP continued to decrease to 3.
2 (IQR 2)
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Another indicator that reflects the status of disease activity, that is, the routine evaluation value of patient data index 3 (RAPID3)* score has also been improved during treatment (Figure 1) [1]
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*RAPID3: It is composed of the self-report score of patients' assessment of their physical function, pain and overall condition
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Figure 1: After abatacept treatment, the changes of DAS28 and RAPID3 in each group from baseline to follow-up treatment.
In addition, during the long-term treatment of abatacept, the functional status of RA patients has also been significantly improved
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In a large-scale multicenter, observational real cohort study, a total of 1771 RA patients treated with abatacept were included (51.
4% of the patients had other comorbidities)
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The results show that whether abatacept is used as a first-line or a late-line biological agent, it can effectively improve the functional status of patients.
The number of treatments (NNT) required to improve the health assessment questionnaire (HAQ) score to achieve the smallest significant change is 1.
4 , The curative effect lasts for two years (Table 1) [2]
.

Table 1: After treatment with abatacept, HAQ changes over time What are the characteristics of the advantageous populations who benefit from treatment with abatacept? The ACTION research points us in the direction
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Consistent with the results of the RCT study, the ACTION study showed that RA patients who were positive for rheumatoid factor (RF) or anti-cyclic citrullinated polypeptide antibody (anti-CCP antibody) were treated with abatacept more significantly
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This study is a 2-year non-interventional international prospective study.
According to the status of patients with RF and anti-CCP antibodies at baseline, the researchers conducted a stratified analysis [3]
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Among patients who were initially treated with biological agents, compared with the RF-negative and anti-CCP antibody-negative groups, the RF-positive and/or anti-CCP antibody-positive groups reached good or moderate European Union for Anti-Rheumatic Diseases (EULAR) after 6 months of treatment A higher proportion of patients responded*, indicating a more significant response to treatment
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*EULAR response standard classifies patients as good, moderate or non-responsive according to the individual change in disease activity score DAS and the level reached by DAS (see Table 2 for details)
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Table 2: EULAR response criteria [4] Figure 2: The EULAR response of patients with different serological status when using abatacept as a first-line biological agent is the same for RA patients treated with biological agents
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The post-hoc analysis of the CERTAIN prospective cohort study showed that if the patient had a high level of anti-CCP2 antibody at baseline, after 6 months of treatment with abatacept, the CDAI score (Clinical Disease Activity Index) had a greater numerical change, and the patient Reported outcomes (PROs) improved more significantly (Figure 3) [5]
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Figure 3: The average improvement in CDAI scores and PROs from baseline in patients in different anti-CCP2 antibody concentration ranges after receiving abatacept treatment (Q1-Q4: different anti-CCP2 antibody concentration ranges, Q1: 11–94 U/ml; Q2: 95–296 U/ml; Q3: 297–876 U/ml; Q4: >876 U/ml) Safety is added to the strong evidence In addition to efficacy, drug safety is also an aspect that cannot be ignored in clinical treatment
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Can the use of abatacept in the treatment of RA achieve both efficacy and safety? Let's take a look at the security data in real-world research
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In the above-mentioned Columbia single-center retrospective cohort study, the investigator analyzed the adverse events (AE) during the treatment process (Table 3)
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91.
8% (146 cases) of patients treated with subcutaneous abatacept had adverse events, but most of them were mild and moderate
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Among them, 74.
2% (118 cases) of patients developed infections during treatment, with the above respiratory tract infections (64%) and urinary tract infections (11%) being the most common
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64.
6% (102 cases) of patients had systemic injection reactions.
Systemic symptoms (such as fever, dizziness, fatigue), headache and gastrointestinal symptoms were the most common.
31.
4% (50 cases) of patients reported local injection site reactions, and most of the reactions The intensity is lighter
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No new case reports of allergic reactions or autoimmune diseases [1]
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Table 3: Safety data of subcutaneous injection of abatacept.
The infection risk of biologics is the main safety consideration in the treatment of clinical RA
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A 10-year analysis of big data studies in the United States shows that compared with TNF-α inhibitors, RA patients treated with abatacept have a lower risk of hospitalization for infection, with a hazard ratio (HR) of 0.
78 (95% CI 0.
64-0.
95) [6] ; Another population-based cohort study showed that compared with other biological agents, when abatacept was used as a first-line biological agent, the risk of severe infection in RA patients did not increase significantly, and the risk of infection during treatment did not increase over time.
The prolongation and change [7]
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These evidences show that the risk of infection with abatacept is relatively low
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In addition, cardiovascular risk is also a concern for patients with RA
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The results of a retrospective cohort study in the United States showed that the risk of acute myocardial infarction (AMI) in RA patients treated with abatacept was 28% lower than that of the TNF-α inhibitor group [8]; the Taiwanese cohort study found that after 2 years of follow-up, The incidence of major adverse cardiac events (MACE) in the rituximab, tocilizumab, and abatacept groups were 7.
17%, 2.
75%, and 2.
38%, respectively (Figure 4)
.

Compared with rituximab, patients in the abatacept group had lower adjusted risks of stroke, heart failure, and MACE, with HRs of 0.
18 (95%CI 0.
05-0.
64, P=0.
008) and 0.
20 (95%CI 0.
05), respectively -0.
83, P=0.
027) and 0.
25 (95%CI 0.
11-0.
55, P＜0.
001) [9]
.

Figure 4: Second-line biologics using rituximab, tocilizumab, and abatacept, the possibility of MACE in each group followed up for 2 years.
In the ACTION study, there were no new or unexpected AEs in the treatment of abatacept
.

Although many patients included in the study had cardiovascular or pulmonary comorbidities at baseline, and 5.
9% of patients had chronic infections (1.
4% of them had tuberculosis), during treatment and follow-up, there were no active tuberculosis cases and only 1 Cases of opportunistic infections, 3 cases of vascular disease (stroke, transient ischemic event, and deep vein thrombosis), 5 cases of severe heart disease, and 7 cases of lung disease
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Regardless of how many TNF-α inhibitors have been used by the patient and regardless of the reason for the failure of their previous treatment, abatacept has relatively good safety and tolerability in real-world RA treatment [10]
.

protracted war? no problem! RA is a chronic disease.
Only continuous and long-term medication can maintain the efficacy, control the disease and improve the prognosis
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Therefore, the evaluation of drug retention rate is very important.
It is a comprehensive indicator that reflects the effectiveness and safety of drugs
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In addition, drug retention rates in real-world studies are also affected by factors such as medical insurance reimbursement policies and doctors' prescription habits
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So, can Abatap stick to this "protracted war"? In the ACTION study, the 2-year survival rate of abatacept for RA treatment was 60.
5% (Figure 5), and the survival rate of the initial treatment group of biological agents was higher than that of the treated group of biological agents (65.
1% vs.
58.
0%) [11]
.

Compared with the retention rate of other biological agents, can the data of Abatacept still beat? Figure 5: In the ACTION study, the retention rate of abatacept within 2 years of treatment compared with other biological agents, the retention rate of abatacept in the real world is still outstanding
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The ANSWER cohort study compared the use of different biologics (including abatacept, adalimumab, pecelizumab, etanercept, golimumab, infliximab, and Tonfliximab) in real-world middle-aged and elderly RA patients.
The duration of medication and the rate of discontinuation of Rizumab
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The study found that after excluding data on discontinuation due to non-drug toxicity and disease remission, the abatacept group had the highest retention rate (Figure 6), and the lowest rate of discontinuation due to lack of efficacy or toxic adverse events [12]
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Figure 6: After multi-factor adjustment, the retention rate of different biological agents (data discontinued due to non-drug toxicity or disease remission is not included) British multi-center, retrospective, observational research findings, and those receiving other biological agents Compared with patients, the average treatment duration of RA patients who used abatacept in the first-line biological therapy was longer (53.
4 months vs.
17.
4 months, P＜0.
01).
After 12, 24, and 36 months of treatment, abatacept The retention rates are 85.
6%, 70.
9%, and 70.
9% respectively (Table 4) [13]
.

Table 4: The duration of initial treatment with different biological agents and the treatment survival rate in different time periods.
In summary, real-world studies reflect the high survival rate of abatacept in the treatment of RA, and its application is conducive to the long-term treatment and management of the disease.
Overcome the "protracted war" of RA treatment
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Summary: The real-world research results of abatacept are consistent with the RCT results, indicating that it has a significant efficacy in the treatment of RA, and has good safety and a high retention rate
.

As a biological agent with a new mechanism, Abatacept has great application potential in the treatment of RA, and we expect it to bring therapeutic benefits to more patients
.

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Subcutaneous abatacept in rheumatoid arthritis: A real-life experience[J].
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[ 2]Pope JE,Rampakakis E,Sampalis J.
The durability of abatacept as a first and subsequent biologic and improvement in HAQ from a large multi-site real-world study[J].
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Baseline autoantibodies preferentially impact abatacept efficacy in patients with rheumatoid arthritis who are biologic naïve: 6-month results from a real-world,international,prospective study[ J].
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[9]Hsieh MJ,Lee CH,Tsai ML,et al.
Biologic Agents Reduce Cardiovascular Events in Rheumatoid Arthritis Not Responsive to Tumour Necrosis Factor Inhibitors:A National Cohort Study.
Can J Cardiol ,2020,36(11):1739-1746.
[10]Nüßlein HG,Alten R, Galeazzi M,et al.
Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year,observational,prospective ACTION study[J].
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[11]Peichl P,Alten R,Galeazzi M,et al.
Abatacept retention and clinical outcomes in Austrian patients with rheumatoid arthritis :real-world data from the 2-year ACTION study[J].
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Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis-The ANSWER cohort study[J].
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