Randomized Controlled Trial in Patients on Long-term Colchicine With Colchicine-resistant Familial Mediterranean Fever (FMF) to Evaluate the Efficacy of On-demand Anakinra Treatment for Painful Attacks in Patients Who Refuse Continuous Daily Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Mean number of FMF-attacks per month at 6 months of treatment.
研究概览
简要总结
To evaluate the efficacy on clinical symptoms in case of FMF attack among FMF patients resistant to Colchicine of
- on demand anakinra treatment (100 mg/d from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) associated with daily colchicine.
- compared to analgesic associated with daily colchicine in patients refusing continuous anti-IL-1 treatment.
详细描述
KIN-ATTACK-FMF will be the first randomized prospective study comparing the efficacy of on-demand anakinra versus standard of care treatment in patients with colchicine resistant symptoms of FMF who refuse continuous daily therapy.
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (100,000 people worldwide and 7500 in France). It causes monthly recurrent febrile abdominal pain with a biological inflammatory syndrome.
To prevent FMF attacks and development of inflammatory amyloidosis (IA) daily oral colchicine is the first line recommended treatment. 10 to 15% of patients are resistant to colchicine: persistence of 1attack/month over a period of 3 months (in spite of taking the maximum tolerated dose of colchicine daily). Subcutaneous anti-interleukin 1 biotherapies were recently allowed in France combined to daily oral colchicine for colchicine resistant FMF: anakinra (short-acting anti-IL1 drug, daily) or canakinumab (long acting monoclonal anti IL1 antibody, every 2 months). These treatments cost respectively 30 and 12,000 euros/injection.
If abdominal attacks are controlled by colchicine, patients still suffer from lower limb pains, particularly erysipelas like erythema and exertional myalgias, which are very disabling and require use of analgesics or anti-inflammatory. However, in the referral center, 20% of colchicine resistant FMF patients don't receive chronic anti IL1 treatment, despite an indication. Main reasons are: 1-they do not want to inject themselves every day (for anakinra); 2-women of childbearing age are afraid about the impact of biotherapies on their fetus; 3-some do not want to ask for 100% coverage because of the biotherapy cost; 4- the authorization for anti IL1 in FMF is very recent and they want more certainty about its effectiveness.
The hypothesis of the study is that on-demand use of Anakinra from onset of attack until 24 hours of remission (during 7 days maximum) associated with chronic daily colchicine as background treatment in case of attack could stop it, thus reducing its length and pain compared to standard of care treatment which includes only classical antalgics with colchicine in patients refusing chronic daily anti IL1 treatment.
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
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 6 years old with no upper limit
- •Proven FMF according to Livneh international criteria and 2 non ambiguous MEFV mutations.
- •Colchicine resistance defined as persistent FMF attack despite the maximum daily posology of colchicine (average one or more attacks per month over a 3-months period)
- •FMF Attack is defined by:
- •Arthritis or
- •Chest pain or
- •Abdominal pain or
- •Myalgia or
- •Erysipelas-like skin lesion Duration of episodes 1-4 days.
- •Patient refusing daily anakinra injections-
- •Patients covered at 100% by the health insurance (ALD)
- •Patient who do not have biological inflammation between attacks
- •Written informed consent of the patients and or his legal representatives
排除标准
- •Evidence of active tuberculosis
- •Infection requiring treatment with intravenous antibiotics within 2 weeks prior to inclusion
- •History of recurrent infection (Need more than 4 courses of antibiotic treatment per year (in children) or more >2 times per year (in adults), experience pneumonia twice over any time or >3 bacterial sinusitis in 1 year)
- •Contraindication to anakinra (Hypersensitivity to the active substance or to any of the excipients (Citric acid, anhydrous Sodium chloride, Disodium edetate dehydrate, Polysorbate 80, Sodium hydroxide, Water for injections ) or to E. coli derived proteins
- •Patients with neutropenia (ANC <1.5 x 10^9/l)
- •Inability to provide informed consent
- •Ongoing chronic treatment with anti IL1 biotherapy since at least 3 months
- •Pregnant women
- •Women in labor and nursing mothers
- •Patients in emergency situations and people hospitalized without consent
- •No health care insurance
- •Contraindication to colchicine
- •Patient participating in another interventional clinical trial
- •Patient deprived of liberty
- •Patient under guardianship or curatorship
- •Patient under court protection
- •Randomization criteria :
- •Absence of active or latent tuberculosis (no tuberculosis sign on chest X-ray and a negative quantiferon)
- •Negative pregnancy test
研究组 & 干预措施
ANAKINRA on Demand
On demand Anakinra 100 mg/j from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) + colchicine + on demand analgesics
干预措施: ANAKINRA (Drug)
结局指标
主要结局
Mean number of FMF-attacks per month at 6 months of treatment.
时间窗: At Months 0 (baseline), Month 1, Month 3 and Month 6
* FMF attacks is defined by a painful (consensual definition) manifestation during 12 to 72 hours, in either : * abdomen (with features consistent with a diagnosis of peritonitis), * chest (with features consistent with a diagnosis of pleuritis), * joints (with features consistent with a diagnosis of lower extremity large joint monoarthritis), * skin (with features consistent with a diagnosis of erysipeloid rash) * The painful manifestation can be (or not) accompanied by fever of ≥ 38°C Patients will be asked to note the number of days of pain of each inflammatory attack on a diary.
次要结局
- Cumulative days of FMF attack treatment from randomization to 6 months(At Months 0 (baseline), Month 1, Month 3 and Month 6)
- AIDAI (Auto-inflammatory Diseases activity index) score(At Months 0 (baseline), Month 1, Month 3 and Month 6)
- Number of painful days and severity of FMF attacks occurring between randomization and M6(At Months 0 (baseline), Month 1, Month 3 and Month 6)
- Quality of life score measured by EuroQOL questionnaire (EQ-5D5L)(At Months 0 (baseline), Month 1, Month 3 and Month 6)
- Number of local cutaneous reactions at 6 months (erythema and oedema involving the injection sites) in the anakinra arm(At Months 0 (baseline), Month 1, Month 3 and Month 6)
- Proportion of Adverse events(At Months 0 (baseline), Month 1, Month 3 and Month 6)