Baricitinib in the Treatment of Intestinal Behçet's Syndrome

The non-inferiority will be established by comparing the lower bound of the two-sided 95% confidence interval with the non-inferiority margin. If the lower bound was larger than the margin, Baricitinib would be regarded as non-inferiror to ADA. Superority will be further assessed in case that the non-inferiority is established. Both ITT and PP analysis will be conducted for the primary outcome given the non-inferiority design. Trial result will be primarily interpreted based on ITT analysis.

Inclusion criteria

• Refer to the consensus on the diagnosis and treatment of intestinal Behçet's syndrome in China: Patients who meet the 2013 International Criteria for Behçet's Disease (ICBD) and have typical Behçet's syndrome-related intestinal ulcers confirmed by colonoscopy, or patients diagnosed according to the criteria for Behçet's syndrome established by the Korean Behçet's Disease Collaborative Group in 2009;
• Patients have a DAIBD score ≥ 40 points or intestinal symptom score ≥ 3 points at baseline;
• Endoscopic examination conducted within 60 days before inclusion suggests active intestinal ulcers;
• Patients who have been treated with medium to high-dose steroids (prednisolone equivalent of 0.5-1 mg/kg/day) for more than 1 month continuously, or any immunomodulator/Immunosuppressants for more than 3 months regularly or biologics for more than 2 months, as judged by the doctor to be treatment failure or intolerance;
• Currently steroid dose ≤ 30 mg prednisolone equivalent, stabilized for ≥ 2 weeks, and/or stabilized immunomodulator dose for ≥ 4 weeks;
• Understanding the research process, voluntary participation, and signing of informed consent.

Exclusion criteria

• Diagnosis of other diseases such as Crohn's disease, ulcerative colitis, lymphoma, etc.;
• Other active organ damage related to BS requires intensified immunosuppressive therapy, including aneurysms, uveitis, and substantial involvement of the central nervous system; skin lesions and joint involvement can be included;
• Severe organ dysfunction including ALT, AST, TBIL levels exceeding twice the upper limit of normal, creatinine levels exceeding 1.5 times the upper limit of normal, white blood cell count < 3×10^9/L, ANC < 2×10^9/L, hemoglobin < 80g/L, platelets < 100×10^9/L;
• Active infections such as active tuberculosis, active hepatitis B or C, syphilis, chronic Epstein-Barr virus infection, HIV infection, sustained or severe bacterial or viral infections, and history of severe herpes zoster;
• Patients with latent tuberculosis must undergo ≥3 weeks of prophylactic anti-tuberculosis treatment before inclusion;
• Primary immunodeficiency disease;
• History of cancer, or endoscopic intestinal histopathology indicating intraepithelial neoplasia or malignancy, or presence of other malignancies;
• Patients who did not respond to infliximab treatment for primary refractory BS (patients with secondary failure, intolerance, or allergy to infliximab should be included);
• Patients treated with biologics/small molecule targeting therapies within 5 half-lives (including use of tofacitinib within 10 days, etanercept within 4 weeks, infliximab within 8 weeks, golimumab, certolizumab, abatacept, and tocilizumab within 10 weeks, ustekinumab within 6 months);
• Patients with prior use of baricitinib or ADA;
• Complications of intestinal BS such as symptomatic stenosis, short bowel syndrome, intestinal fistula, or suspected intra-abdominal abscess; potential need for surgery or situations not conducive to DAIBD and efficacy assessment; any form of intestinal resection or other abdominal surgery within 6 months before baseline; presence of a functioning (i.e., patent) stoma or ostomy;
• Patients requiring parenteral nutrition due to disease severity;
• Pregnant, lactating, or planning pregnancy soon;
• Patients unwilling or unable to comply with regular visits;
• History of severe thrombotic events or chronic cardiovascular events.