Effect of Tofacitinib in Treating ANCA-associated Vasculitis

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.

Inclusion criteria

• 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

Exclusion criteria

• 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.