Methotrexate Combined With Tofacitinib in Rheumatoid Arthritis

Prior treatment

• Patient received conventional synthetic disease modifying anti-rheumatic drugs treatment in the first 12 weeks of randomization
• Patient received biologic agents treatment in the first 6 months of randomization
• Patient received Janus kinase inhibitor treatment before randomization
• Patients with moderate to severe congestive heart failure (New York Heart Association grade III or IV), or recent (within 6 months prior to screening) cerebrovascular accident, myocardial infarction, coronary stent implantation, or uncontrolled hypertension
• Patients with undergone major surgery within the first 4 weeks of randomization, or is expected to undergo major surgery after enrollment; Or a history of chronic pain that may affect the evaluation of the study; Or have received organ transplantation before

Other illness

• Patient with serious diseases under control (such as diabetes), serious respiratory diseases, serious chronic gastrointestinal diseases (such as active or recurrent gastrointestinal ulcers), serious blood system diseases (such as aplastic anemia, myelodysplastic syndrome) or any disease that can cause hemolysis or erythrocyte instability (such as malaria, hemolytic anemia)
• Patients with history of symptomatic herpes zoster infection (within the first 12 weeks of randomization), recurrent or disseminated (even if only once) herpes zoster or disseminated (even if only once) herpes simplex infection
• Chest X-ray or CT examination indicates active tuberculosis, or latent tuberculosis (T-SPOT or TB-IGRA positive) without prophylactic tuberculosis treatment for at least 4 weeks
• Patients woth hepatitis C virus ribonucleic acid (HCV-RNA) testing are higher than the lower limit of detection; Or positive for Treponema pallidum antibody (TP Ab); Or human immunodeficiency virus antibody (HIV Ab) positive during the selected period
• Patients with hepatitis B surface antigen positive without prophylactic antiviral treatment
• Patients with history of lymphoproliferative diseases, or possibly various signs or symptoms of lymphoproliferative diseases
• Patients with any active malignant tumors or history of malignant tumors within the first 5 years, except for skin squamous or basal cell carcinoma, cervical carcinoma in situ, or breast ductal carcinoma in situ that has been treated and considered cured
• Patients with history of thromboembolism, including deep vein thrombosis, pulmonary embolism, arterial thrombosis, etc., or high risk factors prone to thromboembolism (such as obesity, smoking, abnormal coagulation function, diabetes, long-term use of estrogen or use of compound hormonal contraceptives or hormone replacement therapy, long-term braking, etc., which are comprehensively judged by the investigator according to clinical evaluation)
• Patients with history of mental illness, alcoholism, drug or other substance abuse

Lab values

• Patients with blood routine WBC\<4.0 × 109/L, and/or Hb\<90g/L, and/or Plt\<100 × 109/L during the screening period
• Patients with active chronic liver disease or abnormal liver function, AST, ALT, GGT, and TBIL are more than twice the upper limit of normal during the screening period

Other

• Patients with estimated glomerular filtration rate \<30ml/min during screening period
• Pregnant women, lactating women, and men or women who plan to conceive in the near future
• The researchers believe that there are any other factors that may affect the progress or evaluation of the results of this study

• Patients were diagnosed according to the 1987 American College of Rheumatology or 2010 American College of Rheumatology/European League Against Rheumatism criteria
• Patients had moderate or high disease activity
• Patients had a synovial biopsy and with a myeloid-stromal pathotype
• Patients with good compliance, willing to participate in this study and sign an informed consent form