Methotrexate Combined With Tofacitinib in Rheumatoid Arthritis

NCT06301373 | Recruiting

• 1 other identifier: SYSKY-2023-1185-02
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 5

Brief Summary

Rheumatoid arthritis (RA) is the leading cause of disability in Chinese women. We established a synovial pathology queue in the early stage and proposed a new synovial immunopathology classification. We found that baseline myeloid stromal RA patients had severe conditions and poor outcome. Early identification of synovial myeloid stromal RA patients and intensified treatment are key to improving RA efficacy. This project aims to conduct a randomized, controlled, open label, multicenter clinical study on early intensified treatment of RA based on synovial pathology classification. 130 adult patients with synovial myeloid stromal type of primary treatment moderate to severe active RA were planned to be enrolled in three centers: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, and Guangzhou Panyu Central Hospital. They were randomly divided into an intensive treatment group and a conventional treatment group in a 1:1 ratio. The intensive treatment group was treated with methotrexate combined with tofacitinib, while the conventional treatment group was treated with methotrexate monotherapy. The expected intervention period is 12 weeks, with a follow-up period of 48 weeks. The primary endpoint is the proportion of subjects who achieved ACR20 at week 12. Secondary endpoint indicators include improvement in disease activity and joint function among subjects at different follow-up points, safety, and the proportion of subjects who experienced joint destruction progression at week 48. This project proposes the concept of achieving precise diagnosis of RA based on synovial pathology classification, and explores the efficacy of early methotrexate combined with tofacitinib intensified treatment for patients with synovial medullary stromal RA who have poor conventional treatment efficacy, providing high-level clinical evidence for achieving precise initial treatment of RA treatment guidelines.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects who achieved ACR20

  ACR20

  12 week

Secondary Outcomes (10)

• Changes in disease activity scores (DAS28-CRP) relative to baseline

  4, 8, 12, 24, 36, and 48 weeks after treatment

• Changes in disease activity scores (DAS28-ESR) relative to baseline

  4, 8, 12, 24, 36, and 48 weeks after treatment

• Changes in disease activity scores (SDAI) relative to baseline

  4, 8, 12, 24, 36, and 48 weeks after treatment

• Changes in disease activity scores (CDAI) relative to baseline

  4, 8, 12, 24, 36, and 48 weeks after treatment

• Proportion of subjects with low disease activity and remission (SDAI standard) at weeks 4, 8, 12, 24, 36, and 48 after treatment

  4, 8, 12, 24, 36, and 48 weeks after treatment

Other Outcomes (3)

• The proportion of adverse events (AE) in subjects at 4, 8, 12, 24, 36, and 48 weeks after treatment

  4, 8, 12, 24, 36, and 48 weeks after treatment

• The proportion of severe adverse events (SAE) in subjects at 4, 8, 12, 24, 36, and 48 weeks after treatment

  4, 8, 12, 24, 36, and 48 weeks after treatment

• Changes in serum MMP-3 levels relative to baseline

  4, 8, 12, 24, 36, and 48 weeks after treatment

Study Arms (2)

Methotrexate Combined With Tofacitinib

EXPERIMENTAL

Methotrexate 10-15mg orally once a week, tofacitinib 5mg orally twice a day

Drug: Methotrexate Combined With Tofacitinib

Methotrexate

ACTIVE COMPARATOR

Methotrexate 10-15mg orally once a week

Drug: Methotrexate

Interventions

Methotrexate Combined With Tofacitinib DRUG

Methotrexate Combined With Tofacitinib

Also known as: JAK inhibitor

Methotrexate Combined With Tofacitinib

Methotrexate DRUG

Methotrexate

Methotrexate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (5)

Foshan Hopsital of Traditional Chinese Medicine

Foshan, Guangdong, 528000, China

RECRUITING

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 510120, China

RECRUITING

The Affiliated Panyu Central Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 511400, China

RECRUITING

Pu Ning Shi Ren Ming Yi Yuan

Jieyang, Guangdong, 515300, China

RECRUITING

Shenshan Medical Central, Memorial Hospital of Sun Yat-sen University

Shantou, Guangdong, 516621, China

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib; Janus Kinase Inhibitors; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: March 8, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

CN (5)