Faecal Microbiota Transplantation in Patients With Refractory Rheumatoid Arthritis

In this 24-week, single center, randomized, double-blind, placebo-controlled study, the efficacy and safety of lyophilised oral fecal microbiota transplantation in patients with active refractory rheumatoid arthritis will be evaluated.

Inclusion Criteria: 1. Age 18-65 years with informed consent; 2. Fulfill the 2010 ACR/EULAR classification criteria for rheumatoid arthritis; 3. Positive RF or anti-CCP antibody on screening; 4. Active disease status with swollen joint count(SJC)≥3 and tender joint count(TJC)≥3 and ESR \>25 mm/hr or hypersensitive C-reactive protein \> 10 mg/L; 5. Having received csDMARDs including but not limited to methotrexate (at a stable dose of 7.5 - 20 mg/week) for 3 months or longer prior to screening and willing to continue current regimen for the duration of the study; 6. Other csDMARDs (e.g. Leflunomide, Iguratimod, Sulfasalazine, Hydroxychloroquine, Tripterygium Wilfordii, etc.) taking before screening with dosage stablized for 3 months or longer are permitted and should continue during the duration of the study; 7. Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA; 8. If taking non-steroidal anti-inflammatory drugs (NSAIDs), must be at a stable dose for at least two weeks prior to screening; 9. Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses) ; 10. Participants with fertility must use a medically effective form of contraception and agree to continue its use during the study or at least 3 monts after the last dose of study intervention. 11. Willing to suspend the use of other adjuvant treatment for the duration of the study including acupuncture, massage, etc. Exclusion Criteria: 1. Pregnant, lactating or further fertility requirements 2. History of any inflammatory rheumatological disorders other than RA; 3. Having used biologics or small-molecular targeting agents in 6 months prior to screening; 4. Taking oral glucocorticoid (GC) or get GC injection (intra-articular or parenteral) in one month prior to screening; 5. Severe, progressive, or uncontrolled visceral disease including cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease; 6. Severe enteritis, intestinal obstruction or bleeding, or history of gastrointestinal surgery. 7. Active infection in recent 3 months or persistent chronic infection, including HIV, HCV, HBV, tuberculosis; 8. Malignancy or history of malignancy; 8\. Other conditions that investigators consider inappropriate for this study.