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This study includes naive patients and csDMARDs-IR RA patients, treated with different regimens such as Iguratimod combination of different csDMARDs, or csDMARD with TNF inhibitors for 24 weeks. The disease activity and drug response will be observed. The immune disorder and synovial function will be evaluated at the same time.
In this study cohorts, naïve or csDMARDs-IR patients are treated with different csDMARDs combination or TNF inhibitors for 24 weeks to get remission in clinical. The biomarkers in their plasma and synovial fluid and tissue specimens from RA patients are screened to predict the efficacy of specific treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methotrexate(MTX)+Iguratimod(IGU) | Experimental | Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Methotrexate(MTX)，10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. For RA patients with naive or csDMARDs-IR |
|
| Adalimumab+Methotrexate(MTX) | Experimental | Drug: Adalimumab，40mg, iH,q2w, once two weeks (q2w) prescribed at the beginning and adjusted due to patient response. Drug: Methotrexate(MTX)，7-10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. For RA patients with csDMARDs-IR |
|
| Iguratimod(IGU)+Leflunomide(LEF)+Hydroxychloroquine(HCQ) | Experimental | Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Leflunomide(LEF)，20mg, po, quaque day (qd) prescribed at the beginning and adjusted due to patient response. Drug: Hydroxychloroquine(HCQ)，200mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. For RA patients with csDMARDs-IR |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iguratimod | Drug | Iguratimod tablet，25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The percentage of patients who achieve clinical remission using European League Against Rheumatism (EULAR) response criteria DAS28. | The percentage of patients whose Disease Activity Score in 28 Joints (DAS28) achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2). The DAS28 is a composite score derived from 4 of these measures，that is the count of tender joint count（TJC, 0-28）and swollen joint count（SJC, 0-28）, measure erythrocyte sedimentation rate (ESR, mm/h) or C reactive protein (CRP, mg/L) and to make a patient assessment of disease activity i.e. 'global assessment of health' (GH) using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst. DAS28 values were calculated as follows: DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x GH. High disease activity: DAS28-ESR > 5.1; Moderate disease activity: 5.1≥ DAS28 > 3.2 to 5.1; Low disease activity (LDA) and Remission mean Clinical remission. | week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| The percentage of patients who achieve clinical remission using DAS28-ESR. | The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) . | week 12 |
| Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders |
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Inclusion Criteria:
-
1.Patients with RA who meet ACR 1987 rheumatoid arthritis classification criteria or ACR/EULAR 2010 rheumatoid arthritis Classification Criteria and have knee dysfunction.
ACR 1987 rheumatoid arthritis classification criteria
ACR/EULAR 2010 rheumatoid arthritis Classification Criteria
Involved joints
- 1 large joint (0 points)
Serological indicators
Acute chronotropic reactants
Duration of synovitis
<6 weeks (0 points)
≥6 weeks (1 point)
2.Patients with OA who meet the 1995 Classification Criteria for OA and have knee dysfunction 1995 Classification Criteria for Osteoarthritis of the Knee Clinical criteria
a. Knee pain most of the time in the last 1 month b. Bone rubbing sound c, morning stiffness ≤ 30 minutes d, age ≥ 38 years e, with bony enlargement Knee OA can be diagnosed if a+b+c+d or a+b+e is met
3.Age-sex matched healthy volunteers who checked in our hospital.
4.Age > 18 years old;
5.Voluntarily participate in this study and sign an informed consent form
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qiang Shu, Dr. | Contact | 0086-0531-82169654 | shuqiang@sdu.edu.cn | |
| Bingbing Ren | Contact | 0086-18765361979 | sdrenbingbing@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Xiaoyun Yang | Qilu Hospital of Shandong University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Qilu Hospital | Recruiting | Jinan | Shandong | 250012 | China |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C519076 | iguratimod |
| C010169 | glucose utilization inhibitor |
| C077313 | T 614 |
| D008727 | Methotrexate |
| D000068879 | Adalimumab |
| D000077339 | Leflunomide |
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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|
| Methotrexate | Drug | Methotrexate，10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint. |
|
|
| Adalimumab Injection | Drug | Adalimumab Injection，40mg，iH，every two weeks (q2w) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint. |
|
|
| Leflunomide | Drug | Leflunomide，20mg, po, quaque day (qd) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint. |
|
|
| Hydroxychloroquine | Drug | Hydroxychloroquine，200mg, po, twice per day (bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint. |
|
|
△DAS28 indicates the decline of DAS28-ESR from the baseline to week 30. EULAR response states were classified as follows: good responders were patients with an improvement from baseline (△DAS28-ESR) of > 1.2 and a DAS28-ESR at week 30 ≤ 3.2. Moderate responders: △DAS28 > 1.2 and still DAS28 > 3.2 at week 30, or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 30. Nonresponders：△DAS28 ≤0.6 or DAS28 >5.1 at week 30. DAS28-defined remission was classified as a score of <2.6. |
| baseline,week 12,week 24 |
| Percentage of participants achieving ACR/EULAR remission | If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment（PGA） ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease). | week 12,week 24 |
| Change from baseline Simplified Disease Activity Index (SDAI) | The SDAI is a composite score derived from these measures，that is the count of tender joint count（TJC, 0-28）, swollen joint count（SJC, 0-28）, C-reactive protein (CRP, mg/L), Patient global assessment（PGA）and physician global assessment（PHGA）, each of the last two was assessed on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease. SDAI score will be calculated with formula SDAI = TJC + SJC + PGA+PHGA+ CRP. SDAI score exceeding 26 is considered high disease activity; 11 \ | up to week 24 |
| Change from baseline Clinical Disease Activity Index (CDAI) | Change from baseline Clinical Disease Activity Index (CDAI) CDAI is a composite score derived from these measures，that is the count of tender joint count（TJC, 0-28）, swollen joint count（SJC, 0-28）, Patient global assessment（PGA）and physician global assessment（PHGA）, each of the last two was CDAI score will be calculated with formula CDAI = TJC + SJC + PGA + PHGA. CDAI > 22 is considered high disease activity; 10 \ | up to week 24 |
| Change From Baseline in C-reactive Protein (CRP) | Change from Baseline in C-reactive Protein (CRP), a component index of ACR20 and SDAI, CRP will be measured with blood samples. | up to week 24 |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change from Baseline in ESR, that is a component index of ACR20, DAS28-ESR and SDAI, ESR will be measured with blood samples. | up to week 24 |
| Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI) | hange from Baseline in HAQ-DI, a participant assessed measure of health assessment, shaveing eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item on a single scale has 4 degrees ranging from 0 (no functional difficulty) to 3 (unable to do), with higher scores indicating severe disease. | up to week 24 |
| Percentage of American College of Rheumatology [ACR] 20、 [ACR]50、 [ACR]70 Criteria Responders every time | Percentage of American College of Rheumatology [ACR] 20、 [ACR]50、 [ACR]70 Criteria Responders every time. | up to week 24 |
| Incidence of participant withdrawal | Percentage of participants who withdraw from this study. | up to week 24 |
| Number of participants with"adverse events (AEs)" | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with"adverse events (AEs)"i.e. physical exam abnormalities，vital sign abnormalities，laboratory value abnormalities，symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product. | up to week 24 |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |