protocolSection identificationModule nctId: NCT06301373, orgStudyIdInfo id: SYSKY-2023-1185-02, briefTitle: Methotrexate Combined With Tofacitinib in Rheumatoid Arthritis, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2030-04-01, completionDateStruct date: 2030-04-01, studyFirstPostDateStruct date: 2024-03-08, lastUpdatePostDateStruct date: 2024-03-08, sponsorCollaboratorsModule leadSponsor name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, class: OTHER, descriptionModule briefSummary: 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., conditionsModule conditions: Rheumatoid Arthritis, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 130, type: ESTIMATED, armsInterventionsModule interventions name: Methotrexate Combined With Tofacitinib, interventions name: Methotrexate, outcomesModule primaryOutcomes measure: The proportion of subjects who achieved ACR20, secondaryOutcomes measure: Changes in disease activity scores (DAS28-CRP) relative to baseline, secondaryOutcomes measure: Changes in disease activity scores (DAS28-ESR) relative to baseline, secondaryOutcomes measure: Changes in disease activity scores (SDAI) relative to baseline, secondaryOutcomes measure: Changes in disease activity scores (CDAI) relative to baseline, secondaryOutcomes measure: Proportion of subjects with low disease activity and remission (SDAI standard) at weeks 4, 8, 12, 24, 36, and 48 after treatment, secondaryOutcomes measure: The proportion of subjects who met ACR50 criteria at weeks 4, 8, 12, 24, 36, and 48 after treatment, secondaryOutcomes measure: The proportion of subjects who met ACR70 criteria at weeks 4, 8, 12, 24, 36, and 48 after treatment, secondaryOutcomes measure: Changes in the Disability Index (HAQ-DI) of the Health Assessment Questionnaire relative to baseline, secondaryOutcomes measure: Changes in EQ-5D-5L relative to baseline, secondaryOutcomes measure: The proportion of subjects with joint destruction progression at 48 weeks after treatment, otherOutcomes measure: The proportion of adverse events (AE) in subjects at 4, 8, 12, 24, 36, and 48 weeks after treatment, otherOutcomes measure: The proportion of severe adverse events (SAE) in subjects at 4, 8, 12, 24, 36, and 48 weeks after treatment, otherOutcomes measure: Changes in serum MMP-3 levels relative to baseline, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, hasResults: False