Rheumatoid arthritis
Conditions
Interventions
Tofacitinib:Tofacitinib 5mg bid
Tofacitinib With Iguratimod:Tofacitinib 5mg bid With Iguratimod 25mg
Sponsors
The Second Affiliated Hospital of Guangzhou Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Subjects who voluntarily sign an informed consent form before the start of activities related to this research, be able to understand the procedures and methods of this research, and be willing to strictly abide by the clinical research protocol to complete this research;2. The age at the time of signing the informed consent form is 18~75 years old (including both ends), and the gender is not limited; 3. According to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 rheumatoid arthritis (RA) classification criteria,the subjects were diagnosed as RA, and the ACR functional classification was grade I~III at the time of screening;4. Suffering from moderately to severely active RA, defined as 68/66 joint counts, tender joint counts (TJC) = 6 and swollen joint counts (SJC) = 6 at screening and before randomization, and red blood cells at screening Sedimentation rate (ESR) > 28 mm/h or C-reactive protein (CRP) / hypersensitive CRP (hsCRP) > 5 mg/L. Joints that have undergone major surgery are not counted in TJC and SJC;5. Subjects are received at least one of methotrexate, sulfasalazine, leflunomide, and iguratimod (single or combined) for more than 3 months, and the investigator judges that the effect is not good (judging that when the efficacy of methotrexate is not satisfactory, the recommended dose of methotrexate is 10-25 mg/week; the dose of methotrexate <10 mg/week needs to be recorded in the medical record due to safety reasons; such as methotrexate combined with other csDMARDs, When it is judged that the efficacy of methotrexate is not good, there is no requirement for the dose). Poor response can be tender/swollen joint counts, physiological function, or poor response to the doctor's overall assessment of the disease;6. If the subjects are using csDMARDs (including but not limited to methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, penicillamine, gold preparation, minocycline, etc.)alone or less than 2 csDMARDs in combination (combination of methotrexate and leflunomide is not allowed), the subjects should have taken continuous medication for = 3 months and stable dose for = 4 weeks before randomization; if methotrexate is used, the dose should be 7.5~25 mg/week (both ends inclusive). If the subjects did not use csDMARDs other than leflunomide at the time of randomization, they have not used csDMARDs for at least 4 weeks before randomization; they have not used leflunomide for at least 12 weeks before randomization, or use cholestyramine (cholestyramine) to washout for at least 11 days, and discontinuation of cholestyramine for at least 6 hours before randomization;7. If the subjects are taking oral non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesics (such as acetaminophen or weak opioids) alone at the time of randomization, the stable dose is required for =2 weeks before randomization; If the subjects did not take such drugs orally at the time of randomization, they did not take such drugs orally for at least 2 weeks before randomization;8. If the subjects are taking oral glucocorticoids at the time of randomization, the dose should be =10 mg/day of prednisone (or equivalent dose of other glucocorticoids), and it needs to be stable for =4 weeks before randomization; The subjects did not take glucocorticoids orally for at least 4 weeks before randomization;9. Body mass index at screening [BMI=weight (kg)/height2 (m2)] = 18 kg/m2.
Exclusion criteria
Exclusion criteria: 1. General situation: 1) pregnant or breastfeeding women; 2) No contraceptive use or refusal to use contraceptive measures within 28 days from the screening period to the last dose (except for the subject or partner who is infertile);3) drug abuse;4) The investigator judges that there is a situation that affects the evaluation of drug safety and efficacy;2. Within 4 weeks prior to the visit, the following conditions were present on laboratory tests and 12-lead ECG:1) White blood cell count the upper limit of normal;6) The estimated glomerular filtration rate (eGFR) calculated by the simplified dietary modification for renal disease (MDRD) formula is less than 60 mL/min/1.73 m2;7) Glycated hemoglobin (HbA1c) = 8.0%; 8) Anti-hepatitis C virus antibody, human immunodeficiency virus antibody, and Treponema pallidum antibody test are positive, and the exclusion criteria for hepatitis B virus (HBV) infection are as follows: Hepatitis B surface antigen (HBsAg) positive; or HBsAg negative, hepatitis B Core antibody (HBcAb) positive and hepatitis B surface antibody (HbsAb) negative, further test positive for hepatitis B virus deoxyribonucleic acid (HBV-DNA);9) The 12-lead ECG indicates clinically significant abnormalities that may affect the safety of the subject, including but not limited to acute myocardial ischemia, myocardial infarction, severe arrhythmia or significant QTc prolongation (QTc>500 ms);3. Presence of any of the following medical history or comorbidities:1) Allergic to the study drug or any ingredient in it;2) Having any other systemic inflammatory disease or autoimmune disease other than RA (except secondary Sj?gren's syndrome), including but not limited to psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, systemic Lupus erythematosus, scleroderma or polymyositis, multiple sclerosis and other central demyelinating diseases, primary Sj?gren's syndrome, immunodeficiency syndrome (such as Ferty), etc.;3) Tuberculosis (TB) or occult TB infection (one of the following conditions is met): Active TB or symptoms of active TB at screening or physical examination suggestive of active TB or interferon-gamma release test within 4 weeks before randomization Positive or imaging examinations within 3 months before screening suggest signs of active TB; 4) History of non-tuberculous mycobacteria infection or opportunistic pathogen infection (such as cytomegalovirus, Pneumocystis Aspergillus infection, etc.) within 6 months before screening; 5) History of recurrent herpes zoster (= 2 times), disseminated herpes zoster or disseminated herpes simplex;6) Potential or ongoing granulomatous inflammation, such as histoplasmosis, coccidioidomycosis, etc.;7) History of chronic infection requiring treatment (such as chronic bronchitis, chronic renal pelvis, etc.) within 12 months before screening;8) History of infection (viral, bacterial, fungal, parasitic infection) within 3 months before randomization, hospitalization, and/or parenteral systemic antimicrobial therapy; systemic antimicrobial therapy used within 2 weeks before randomization a history of infection; or an open draining wound or ulcer at screening; or a joint prosthesis infection;9) History of lymphoproliferative diseases, such as lymphoma; or the presence of various signs or s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ACR20; | — |
Secondary
| Measure | Time frame |
|---|---|
| ACR50;ACR70;HAQ-DI;SF-36; | — |
Countries
China
Contacts
Public ContactHuang WenHui
The Second Affiliated Hospital of Guangzhou Medical University
Outcome results
None listed