Methotrexate plus tofacitinib for rheumatoid arthritis
Methotrexate Combined With Tofacitinib in the Treatment of Active Rheumatoid Arthritis With a Myeloid-stromal Pathotype: a Randomized, Controlled, Open Label, Multicenter Clinical Study
NA · Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · NCT06301373
This project will test whether adding tofacitinib to methotrexate helps adults with early, moderate-to-severe rheumatoid arthritis who have a myeloid-stromal synovial pattern.
Quick facts
| Phase | NA |
|---|---|
| Study type | Interventional |
| Enrollment | 130 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other) |
| Drugs / interventions | tofacitinib, methotrexate, Barretinib, Upatinib |
| Locations | 5 sites (Foshan, Guangdong and 4 other locations) |
| Trial ID | NCT06301373 on ClinicalTrials.gov |
What this trial studies
This is a randomized, open-label, multicenter trial enrolling about 130 adults with moderate-to-severe primary rheumatoid arthritis whose synovial biopsy shows a myeloid-stromal pathotype. Participants are randomized to an intensive treatment arm receiving methotrexate plus tofacitinib or to a conventional arm receiving methotrexate alone, with clinical and imaging follow-up to compare outcomes. Trial enrollment is limited to patients identified by synovial immunopathology at three hospitals in Guangdong, China. The aim is to determine whether early intensified, pathology-guided therapy reduces progression and improves response compared with standard methotrexate care.
Who should consider this trial
Good fit: Adults with early, moderate-to-severe rheumatoid arthritis who have undergone synovial biopsy showing a myeloid-stromal pathotype and who are appropriate candidates for methotrexate-based therapy.
Not a fit: Patients without the myeloid-stromal synovial pattern, those with long-established disease, prior exposure to JAK inhibitors or biologics, or with serious uncontrolled comorbidities are unlikely to benefit from this targeted intensified approach.
Why it matters
Potential benefit: If successful, this approach could reduce early joint damage and improve treatment response by tailoring therapy to synovial pathology.
How similar studies have performed: Combining JAK inhibitors like tofacitinib with methotrexate has demonstrated efficacy in RA, but using synovial immunopathology to guide early intensified therapy is a novel approach with limited prior clinical testing.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * 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 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 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 * Patients with estimated glomerular filtration rate \<30ml/min during screening period * 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 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 * Patients with history of mental illness, alcoholism, drug or other substance abuse * 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
Where this trial is running
Foshan, Guangdong and 4 other locations
- Foshan Hopsital of Traditional Chinese Medicine — Foshan, Guangdong, China (RECRUITING)
- Sun Yat-sen Memorial Hospital — Guangzhou, Guangdong, China (RECRUITING)
- The Affiliated Panyu Central Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (RECRUITING)
- Pu Ning Shi Ren Ming Yi Yuan — Jieyang, Guangdong, China (RECRUITING)
- Shenshan Medical Central, Memorial Hospital of Sun Yat-sen University — Shantou, Guangdong, China (RECRUITING)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Rheumatoid Arthritis