Infliximab Therapy in Patients With Refractory Polymyalgia Rheumatica: a Double Blind Placebo Controlled Trial
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Proportion of responders(complete remission without corticosteroids)
研究概览
简要总结
Rheumatic Polymyalgia(PMR) is a relatively common chronic inflammatory disorder of unknown origin which predominantly develops in elderly subjects and presents with severe pain and stiffness in the neck, shoulder and pelvic girdles, along with increased acute phase reactants. Systemic manifestations such as fever, anorexia and weight loss are characteristic signatures of PMR.
Corticosteroids (CS) constitute the standard treatment of PMR. Although in most patients the symptoms of the disease disappear after one or two years of treatment, a proportion of patients remain CS-dependent with the subsequent CS toxicity. Open label studies have suggested that tumour necrosis factor (TNF) antagonists lead to sustained improvement and CS sparing effect in patients with refractory PMR.
The investigators conducted a randomised, double-blind, placebo controlled trial with infliximab in CS-dependent patients with PMR. Patients with CS-dependent PMR (defined as requiring ≥ 5 mg/day after at least 2 years of treatment to maintain remission or ≥ 7.5 mg/day after at least 6 months) were randomly assigned to receive Infliximab (5 mg/kg i.v) at 0, 2, 6, 14 and 22 weeks (n = 12) or placebo (n = 11) together with CS that were reduced according to a predefined schedule. The primary outcome was the proportion of responder patients -defined as individuals with both complete clinical and analytical remission without receiving CS for at least three months- at 24 weeks. Secondary outcomes were cumulative CS doses and adverse events proportion.
详细描述
The duration of the study will be 1 year, and it will be divided in several phases:
A) Initial phase (double-blind trial): Between week 0 and week 24. Placebo or Infliximab at a dose of 3 mg/kg/day at weeks 0, 2 and 6.
After the screening process, patients who meet the inclusion/exclusion criteria of the protocol will be randomized to receive three infusions of placebo or infliximab as previously described.
After the first infusion (week 0), the prednisone dose will be tapered according to the following schedule: Prednisone (or equivalent) should be decreased at a rate of 1.25 mg per week until complete withdrawal of corticosteroids. In case of relapse, the dose of prednisone will be increased up to the previous dose that controlled the symptoms of PMR, and after 4 weeks of stable dose, prednisone will be again tapered but with a slower schedule: 1.25 mg every 2 weeks until complete withdrawal of corticosteroids. In case of a new relapse, the dose of prednisone will be managed according to the physician criteria.
B) Extension phase (open trial): Between week 24 and week 48. Infliximab at a dose of 3 mg/kg/day at weeks 24, 26 and 30.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PMR patients that after 2 years of corticosteroid treatment are not able to reduce the dose of prednisone below 5 mg/day or equivalent.
- •PMR patients that after 6 months of corticosteroid treatment are not able to reduce the dose of prednisone below 7,5 mg/day or equivalent.
- •PMR patients should fulfill the criteria proposed by Chuang et al (8):
- •Age ≥ of 50 years.
- •Development of bilateral moderately/severe aching and stiffness persisting for 1 month or more, involving two of the following areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs.
- •ESR ≥ 40 mm/h.
- •Complete clinical response to low-dose of steroids (prednisone or equivalent ≤ 20mg/day)
排除标准
- •-Patients with biopsy-proven GCA or those with cranial symptoms or signs suggestive of GCA but without biopsy-proven arteritis.
- •Patients with clinical features suggestive of RA or other connective tissue disorders.
- •Chronic infections such as HIV, hepatitis B or C, active mycobacterial or fungal infections, etc.
- •Neoplasm or a history of malignancy in the preceding 5 years.
- •Patients with multiple sclerosis or other demilinizating disorders.
- •Patients with cytopenias: leukopenia (leukocytes ≤ 3.5x109/L.), thrombocytopenia (platelets ≤ 100x109/L.) and/or anemia (≤ 10 g./dl.)
- •Patients with cardiac failure (functional class III / IV).
- •Any other condition that contraindicates Infliximab therapy
研究组 & 干预措施
infliximab
干预措施: infliximab (Drug)
inactive powder
干预措施: inactive powder (Drug)
结局指标
主要结局
Proportion of responders(complete remission without corticosteroids)
时间窗: at 24 weeks
次要结局
- Cumulative dose and side effects of steroids(at 24 and 48 weeks)
- Proportion of responders(at 48 weeks)
- Number of patients that should be re-treated with infliximab(48 weeks)
- Side effects of Infliximab in this patient population(48 weeks)
- Time to response(48 weeks)
- Response duration(48 weeks)
- Number of relapses / recurrences(48 weeks)
研究者
Dr. Vicente Rodri-guez Valverde
Rheumatology, MD, PhD
Hospital Universitario Marqués de Valdecilla