Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission: a Prospective, Pilot Study.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The percentage of patients maintaining the off-therapy clinical remission over the follow-up as expressed by absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination
研究概览
简要总结
Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been found to have a crucial role in the pathogenesis of Giant cel arteritis (GCA). Based on this rationale, several recent studies demonstrated the efficacy of tocilizumab (TCZ), an anti-IL-6 targeted monoclonal antibody, for the treatment of patients with refractory GCA. Confirming previous reports,in a recent retrospective study the investigators successfully treated 10 patient with refractory GCA with TCZ. All patients achieved a complete disease remission evaluated by clinical, laboratory, and positron emission tomography (PET). In a considerable number of GCA patients treated with corticosteroids (CS) the therapy may be interrupted with no disease flares. No data are available on the management of patients achieving the remission with TCZ.
详细描述
Study design. Open-label, prospective, pilot study on patients with giant cell arteritis (GCA) resistant to corticosteroids (CS) .
Setting. Rheumatology department, Hospital of Prato, Prato, Italy. Treatment. All refractory GCA patients with or without involvement of aorta and its thoracic branches treated with intravenous TCZ at the dose of 8 mg/Kg/monthly or subcutaneous TCZ at the dose of 162 mg/weekly who achieved a stable remission over a 6-month period should receive reduced TCZ doses with the following schedules: intravenous TCZ tapering to 2 mg/Kg/monthly with drug withdrawal at month 4, and subcutaneous TCZ monthly reduction through the lengthening of injection intervals every 2, 3 , and 4 weeks, and with drug interruption at month 4.
Primary end-point. To investigate the maintenance of clinical remission after TCZ interruption over a 6-month follow-up period.
Secondary end-points. To assess the maintenance of clinical remission during the treatment, to evaluate the role of acute-phase reactants and PET in predicting the relapse and remission, and to assess the occurrence of adverse event (AEs).
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All consecutive patients meeting the 1990 ACR classification criteria for GCA.
排除标准
- •Corticosteroid treatment during the previous 6 months.
- •Uncontrolled diabetes.
- •Uncontrolled hypertension.
- •History of cancer within the past 5 years.
- •History of frequent infections in the past.
- •Positivity of screening procedures for latent tuberculosis infection.
- •Uncontrolled dyslipidemia at baseline.
- •Known intestinal diverticulosis.
- •Concomitant hematologic disorders.
研究组 & 干预措施
Patients with GCA (ACR 1990 criteria)
At diagnosis, all GCA patients with or without involvement of aorta and its thoracic branches will receive PDN 50 mg/day and TCZ 8 mg/Kg/iv monthly. In all patients PDN dose will be reduced of 10 mg every 2 weeks until interruption at week 12.
Week 12. Subcutaneous TCZ 162 mg/weekly will be administered for additional 12 weeks.
Week 24. TCZ tapering every 8 weeks as follows:
- 1 injection every 2 weeks
- 1 injection every 3 weeks
- 1 injection every 4 weeks Week 48. TCZ withdrawal. Week 72. Remission evaluation.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
The percentage of patients maintaining the off-therapy clinical remission over the follow-up as expressed by absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination
时间窗: 6-month off-therapy period
ESR ≤15 mm/h; CRP ≤0.5 mg/dl; VAS pain ≤10; PET: normalized SUVmax ≤1
次要结局
- The percentage of patients achieving and maintaining the clinical remission during the treatment with TCZ as expressed by the absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination(12 months)
- To compare the role of acute-phase reactants and 18F-FDG-PET in the evaluation of remission.(Months 6,12,18)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0" MeDRA 12.1.(Month 18)
研究者
Fabrizio Cantini
Director of the Dpt. of Rheumatology
Hospital of Prato