The clinical medication problems of patients with refractory RA. Does this case have any enlightenment for you?

*It is only for medical professionals to read and refer to refractory, but not without solution.
Rheumatoid arthritis (RA) is a common chronic progressive disease in rheumatology and immunology.
Its early clinical manifestations are not obvious, but as the course of the disease is prolonged and the disease progresses, Patients may gradually experience cartilage and bone destruction, leading to joint deformities and dysfunction.

As an autoantibody, anti-cyclic citrullinated peptide (CCP) antibody has high sensitivity and specificity for the early diagnosis of RA.

Studies have pointed out that the positive anti-CCP antibody is related to the degree of bone and joint destruction.
The higher the titer, the faster the patient's bone erosion progresses.

Therefore, high titers of anti-CCP antibodies are one of the predictors of poor prognosis in RA patients [1].

my country's data shows that even if more than 80% of RA patients are treated with disease-improving anti-rheumatic drugs (DMARDs), the proportion that can achieve clinical remission is still less than 30% [2].

For patients with refractory RA, the treatment achievement rate or remission rate is lower, and the choice of treatment drugs is more difficult.

So, how should we adjust the treatment plan for these refractory RA patients? In this issue, we invited Dr.
Gu Liyang from the Department of Rheumatology and Immunology, Renji Hospital, Shanghai Jiaotong University School of Medicine, to introduce a case of abatacept in the treatment of refractory RA.

Classic case first look at the basic situation of the patient: female, 76 years old Chief complaint: multi-joint swelling and pain 5 years current medical history: at the end of 2015, multi-joint swelling and pain in the hands/foot with low fever (37.
5℃), check ESR and C-reaction The protein (CRP) level rises, the anti-CCP antibody is positive, and the diagnosis is RA; for the specific treatment process, see the following "Previous Treatment Plan and Efficacy".

He was admitted to the hospital on October 27, 2020.

Past medical history: T11 vertebroplasty due to trauma in 2017; history of herpes zoster in September 2018; denial of history of hypertension, diabetes, and history of smoking and drinking.

Admission examination: body temperature (T) 36.
2℃, pulse (P) 82 beats/min, breathing (R) 20 beats/min, blood pressure (BP) 158/84 mmHg.

Refreshing, good spirits, superficial lymph node enlargement, heart rhythm, no murmur, clear breath sounds in both lungs, no dry and wet rales, soft abdomen, no tenderness, no rebound pain, liver, spleen, and lower ribs And, the lower limbs are swollen.

S+T++ for both hands joints and S++T++ for both knee joints.

Laboratory examination: ① Blood routine: white blood cells (WBC) 13.
16×109/L↑, neutrophils (N) 87.
1%↑, hemoglobin (HB) 97g/L↓, platelets (PLT) 527×109/L↑; ②Biochemical: albumin 32.
7g/L↓, alanine aminotransferase (ALT) 18 IU/L, aspartate aminotransferase (AST) 19 U/L, lactate dehydrogenase 260 U/L↑, total bilirubin 8.
1 μmol/L , Creatinine 81 μmol/L; ③ Autoantibody: rheumatoid factor (RF) 6370 IU/ml↑, anti-CCP antibody>300.
0 U/ml; ④Inflammation indicators: ESR 101.
00 mm/H↑, CRP 150.
57 mg/L↑.

Admission diagnosis: RA (high disease activity, DAS28-CRP is 5.
96), osteoporosis, thoracic vertebral fractureplasty, treatment process and curative effect of herpes sequelae Figure 1: The patient's previous treatment process • In 2015, he was diagnosed with RA .Treated with prednisone acetate (Pred) + leflunomide (LEF) + methotrexate (MTX), no significant relief of joint symptoms; • March 2016, combined with etanercept 25 mg biw for 3 months , The effect is not good; • In May 2016, he was given tocilizumab 480 mg intravenously, once a month, and the joint swelling and pain was relieved; • In July 2017, the left lower limb soft tissue infection occurred, and tocilizumab was discontinued Anti-infective treatment was taken and the condition improved; • In August 2017, the combined use of MTX 10 mg qw + Iguratimod (IGU) 25 mg qd + LEF 10 mg qd + Pred 10 mg qd, the follow-up condition remained stable, and the hormones gradually Reduce to 5 mg qd and stop LEF; • In 2019, the condition will be active again, and the treatment plan will be adjusted to Pred 10 mg qd+MTX 10 mg qw + IGU 25 mg bid + Tripterygium wilfordii 10 mg tid; • April 2020, joint swelling The pain worsened, and he was treated with adalimumab (ADA) 40 mg q2w in July.
After four times of use, he developed fever (T 38.
5°C) and herpes zoster.

After stopping ADA, joint swelling and pain and edema of both lower extremities recurred.

Table 1: Changes in some efficacy indicators in previous treatments TJC: number of tender joints; SJC: number of swollen joints; PGA: doctors overall assessment of the current treatment plan and efficacy: starting from October 30, 2020, add abatacept 125 mg qw Subcutaneous injection, while maintaining Pred + IGU + Tripterygium wilfordii treatment, and then gradually discontinuing Tripterygium wilfordii and hormone reduction.

At present, the patient continues to use abatacept and is in the process of reducing the dose.
His condition fluctuates but the control is basically stable.

And the patient is well tolerated, and there is no obvious adverse drug reaction.

Table 2: Changes in related efficacy indicators after admission to hospital.
VAS: Introduction to the experts of visual analog scoring method.
Dr.
Gu Liyang, attending physician in the Department of Rheumatology and Immunology, Renji Hospital, graduated from Shanghai Jiaotong University School of Medicine in 2011, majoring in clinical medicine, and engaged in clinical front-line work.
He specialized in arthritis, published several medical papers, and presided over a municipal-level project.
Although Dr.
Gu Liyang usually treats RA that cannot effectively alleviate the condition after a regular course of foot treatment or has recurring attacks and progressive joint destruction as difficult in clinical practice.
Therapeutic RA[3].

However, the academic circle still lacks authoritative and unified standards for its accurate definition.

At the 2020 Asia Pacific Association of Rheumatology Association (APLAR) Annual Meeting, researchers used a cross-sectional study to analyze the clinical characteristics of patients with refractory RA, and summarized the following 5 characteristics: advanced age, female, RF positive, anti- CCP antibody positive and long course of disease [4].

In 2021, the European Union Against Rheumatism (EULAR) proposed that refractory RA should meet the following three criteria[5]: ①Treatment failure history: After the failure of traditional synthetic DMARDs (csDMARDs) treatment (unless there are contraindications), there is ≥2 Two kinds of biological agents with different mechanisms of action or targeted synthetic DMARDs have failed treatment; ②There is at least one of the following clinical manifestations that indicate disease activity or progression: disease activity ≥ moderate, with features indicating that the disease is in an active phase (including acute phase reactions) Physical and imaging findings) and/or symptoms, inability to stop glucocorticoids, rapid imaging progress, or none of the above four conditions, but there are still symptoms that lead to a decline in quality of life; ③Clinical cognition: rheumatologist immunologist And (or) patients find it difficult to manage symptoms and (or) signs.

This patient fully meets the five characteristics summarized in the above-mentioned study, and also meets the three criteria defined by EULAR.
Under previous conventional therapies such as csDMARDs and two kinds of biological agents with different mechanisms of action, they have not obtained good disease control or have obvious adverse effects In response, the disease activity (DAS28-CRP) was high at the time of admission, the anti-CCP antibody titer was high, the joint damage was more serious, and the condition was repeated and difficult to control.

In addition, the patient is older, and the adverse drug reactions limit the choice of treatment options.
It is a typical refractory RA patient. Considering that patients have used tumor necrosis factor-α (TNF-α) inhibitors, interleukin-6 (IL-6) receptor antagonists and have poor effects or have obvious adverse reactions, abatacept has different effects Mechanism of biological agents, by regulating T cell costimulatory signals to weaken the immune response and inflammatory response, is suitable for the treatment of active RA; and the incidence of severe infection of abatacept is lower than other biological agents, and the safety is better.

Previous studies have shown that abatacept has a good effect in the treatment of RA patients who do not respond well to conventional regimens such as MTX and TNF-α inhibitors.
It can not only relieve disease symptoms and reduce disease activity, but also delay the progress of imaging.
Higher drug retention rate [6-9].

In addition, the treatment response rate of abatacept is related to the titer of anti-CCP antibody.
For RA patients with high titers of anti-CCP antibody, abatacept can effectively improve related indicators and symptoms, thereby achieving a better treatment outcome [10-13 ].

After treatment with Abatacept for more than a month in this patient, inflammatory indicators such as CRP and ESR decreased significantly, joint swelling and pain (SJC, TJC) were improved, and disease activity was controlled; and so far no obvious adverse reactions occurred, and his health was in good condition.

At present, the patient's condition is basically stable, and he is in the stage of gradual reduction of biological agents.

Therefore, through the treatment process of this patient, we can see that abatacept has both efficacy and safety, or a more feasible medication regimen for the treatment of refractory RA.

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