Difficult-to-treat Rheumatoid Arthritis
Conditions
Interventions
Kunxian Capsule group:Kunxian Capsules (0.3 g per capsule, orally, 2 capsules each time, 3 times daily) in combination with methotrexate (10-15 mg per week) and tofacitinib (5 mg, twice daily), for a
followed by another 12 weeks of the same regimen for maintenance therapy.
Placebo group:The simulated Kunxian capsule (appearance and odor consistent with the genuine drug, oral administration, 2 capsules per dose, 3 times daily) was used in combination with methotrexate (1
the subsequent 12 weeks were modified to continue treatment with Kunxian capsules in combination with methotrexate and tofacitinib.
Sponsors
Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
Eligibility
Sex/Gender
All
Age
50 Years to 70 Years
Inclusion criteria
Inclusion criteria: Subjects must meet the following criteria to be eligible for this study: 1. Fully understand the purpose and requirements of this trial, voluntarily participate and sign a written informed consent, and voluntarily accept and be able to complete the study process, including medication and follow-up examinations. 2. Male subjects aged =50 years without reproductive needs or postmenopausal female patients, with an age less than 70 years. 3. Patients diagnosed with rheumatoid arthritis (RA) according to the 1987 revised criteria of the American College of Rheumatology (ACR) or the 2010 classification criteria of the ACR/European Alliance of Associations for Rheumatology (ACR/EULAR). 4. RA patients with symptoms of (rheumatic obstruction), characterized by: - Main symptoms: joint pain, swelling, migratory; joint pain, swelling, intermittent. - Secondary symptoms: aversion to wind, sweating; headache; heavy limbs. - Tongue and pulse: pale red tongue, thin white coating, slippery or floating pulse. Diagnosis of (rheumatic obstruction) can be made with 2 main symptoms, or 1 main symptom and 2 secondary symptoms, combined with tongue and pulse findings. 5. Confirmed as moderate to severe active RA, defined as follows at screening: - =6 tender joints (TJC) (based on a 68-joint count) and =6 swollen joints (SJC) (based on a 66-joint count), - Erythrocyte sedimentation rate (ESR) >28 mm/h or C-reactive protein (CRP) >10 mg/L, - And DAS28-CRP >3.2. 6. Previous use of 2 different disease-modifying antirheumatic drug (DMARD) treatment regimens for RA (excluding the regimen of methotrexate + JAK inhibitor + Qunxian capsules), with each regimen showing inadequate response (DAS28-ESR >3.2) after at least 12 weeks of treatment.
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will be excluded from the study: 1. History of suspected or confirmed allergy to the investigational product (including excipients or drugs of the same class), or other severe allergic conditions (excluding the disease under study) deemed by the investigator to potentially compromise the subject's safety. 2. Inflammatory diseases other than RA, including but not limited to psoriatic arthritis, ankylosing spondylitis, and systemic lupus erythematosus. 3. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases; history of venous thromboembolic disease, diverticulitis, significant dyslipidemia, or poorly controlled dyslipidemia. 4. History of lymphoproliferative disease upon inquiry; or current or history of malignancy. 5. Meeting any of the following tuberculosis (TB) screening criteria for exclusion: a. History of active TB; b. Recent close contact with an individual with active TB; c. Symptoms or signs suggestive of active TB based on medical history and physical examination; d. Chest CT scan within 3 months prior to enrollment showing evidence of active pulmonary TB; e. Positive interferon-gamma release assay for TB within 6 weeks prior to enrollment. 6. Presence of active infection or relevant history: a. Systemic anti-infective therapy within 4 weeks prior to randomization; b. Sore throat, nasal congestion, acute upper respiratory tract infection, or systemic acute infection within 2 weeks prior to randomization; c. Presence of recurrent, chronic, or other active infections at screening, which, in the investigator's judgment, could increase the subject's risk. 7. History of recurrent herpes zoster, disseminated herpes zoster, or disseminated herpes simplex; or history of herpes zoster or herpes simplex within 2 months prior to randomization. 8. Positive hepatitis B surface antigen (HBsAg) and/or HBV DNA > 50 IU/mL (or > 500 copies/mL) at screening; positive hepatitis C virus antibody (HCV Ab), positive human immunodeficiency virus (HIV) antibody, or positive anti-Treponema pallidum antibody at screening. 9. Administration or planned administration of live or attenuated vaccines within 3 months prior to the first dose of the investigational product, during the study, or within 6 months after the last dose. 10. Pregnant or lactating women, or subjects planning pregnancy or fathering a child during the study period or within 6 months after the study completion; or subjects with childbearing potential who have fertility requirements. 11. Clinically significant abnormalities in 12-lead ECG at screening that, in the investigator's opinion, may increase the subject's risk. 12. Presence of any other disease at screening that may interfere with the study evaluation. 13. Any of the following laboratory abnormalities at screening: a) Hemoglobin < 100.0 g/L (male) or < 90.0 g/L (female); b) Total white blood cell count (WBC) < 4.0 x 10^9/L; c) Neutrophil count (NEUT) < 1.5 x 10^9/L; d) Platelet count (PLT) < 100 x 10^9/L; e) Lymphocyte count (LYMPH) < 0.5 x 10^9/L; f) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), or serum creatinine (Scr) above the upper limit of normal; g) Abnormalities in complete blood count, liver function, or renal function, which, based on the investigator's asse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The achievement rate of the American College of Rheumatology's 20% improvement criteria at week 12.; | — |
Secondary
| Measure | Time frame |
|---|---|
| The achievement rate of the 50% and 70% improvement criteria of the American College of Rheumatology.;Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate Change;Health Assessment Questionnaire-Disability Index Change;Change in TCM syndrome score; | — |
Countries
People's Republic of China
Contacts
Public ContactHe Dongyi
Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
Outcome results
None listed