Tofacitinib for the Treatment of Anti-Neutrophil Cytoplasm Antibody-associated Vasculitis: a Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- The response rate (CR, PR and TR)
研究概览
简要总结
The goal of this study is to evaluate the efficacy and safety of tofacitinib 5 mg twice daily in AAV patients.
详细描述
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. The predominantly used treatment for induction of remission in AAV consisted of cyclophosphamide (CYC) plus corticosteroids (GCs) which leads to remission in about 90% of patients. However, relapses are frequent and remain a challenge. The optimal drug for maintenance treatment is not determined. Tofacitinib is a Jak inhibitor which has been proved to be effective in multiple inflammatory diseases such as rheumatoid arthritis. Considering that T cells and associated cytokine production play an important role in the pathogenesis of AAV via activation of the JAK/ STAT pathway, we hypothesized that tofacitinib-mediated inhibition of JAK signaling may represent an effective therapy for active AAV. In this prospective, open label, single arm study, tofacitinib 5mg twice a day will be added to the background treatment of GCs and immunosuppressants in AAV, the safety and efficacy of tofacitinib will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active AAV met the criteria of 1990 ACR and 2012 Chapel Hill criteria
- •Age 18 to 75 years
- •Written informed consent obtained before taking part in the study
排除标准
- •Severe AAV defined as potentially organ- or life-threatening disease (i.e. alveolar haemorrhage, heart failure caused by myocarditis or pericarditis, progressive neurological symptoms, deaf, blindness, et al.)
- •Serum creatinine>120umol/L or proteinuria>1.0g/d
- •Receipt of a JAKi therapy previously
- •Co-existence of another systemic autoimmune disease
- •Secondary vasculitis (following neoplastic disease, an infection or antithyroid drugs)
- •Malignancy or history of malignancy
- •Infection by HIV, HCV, HBV or tuberculosis-
- •Severe uncontrolled cardiovascular, pulmonary, liver, gastrointestinal, endocrine, hematological, neurological, or psychiatric diseases that are not related to systemic vasculitis
- •Allergic to JAKi
- •Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.5 x 109/L; Platelet count <100 x 109/L; Alanine transaminase or aspartate aminotransferase or total bilirubin>1.5 upper normal limit; Estimated glomerular filtration rate<60ml/min/1.73m2
- •Incapacity or refusal to understand or sign the informed consent form.
- •Pregnancy, breastfeeding.
研究组 & 干预措施
Tofactitinib
Tofacitinib 5mg twice a day
干预措施: Tofacitinib (Drug)
结局指标
主要结局
The response rate (CR, PR and TR)
时间窗: From the enrollment to the end of follow-up [0 to 13 months.]
The percent of patients who achieved disease response. The disease response includes:(1) complete remission (CR), defined as the absence of disease activity (BVAS = 0); (2) partial remission (PR) defined as at least 50% reduction of BVAS and no new manifestations; (3) treatment resistance (TR) was defined as less than a 50% reduction or increased disease activity after 4 \~ 6 weeks of treatment.
次要结局
- Changes in CRP(From the enrollment to the end of follow-up [0 to 13 months].)
- The rate of adverse event(From the enrollment to the end of follow-up [0 to 13 months].)
- Changes in erythrocyte sedimentation rate (ESR)(From the enrollment to the end of follow-up [0 to 13 months].)
- Changes in glucocorticoids steroids (GCs) dosage(From the enrollment to the end of follow-up [0 to 13 months].)