CHronic Nonbacterial Osteomyelitis International Registry (CHOIR)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- The change of CNO disease activity score
研究概览
简要总结
The objective of the study is to establish a prospective disease registry for chronic recurrent multifocal osteomyelitis (CRMO)/chronic nonbacterial osteomyelitis (CNO) in order to investigate the natural history of the disease and the responses of patients to different clinical managements over 10 years.
详细描述
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that mainly affects children and adolescents. Clinical presentations range from mild and sometimes limited unifocal disease to severe, chronically active or recurrent inflammation of multiple bones. The latter is referred to as chronic recurrent multifocal osteomyelitis (CRMO). Here we will use the term "CNO" to refer to the entire spectrum of this disease. CNO can be complicated by vertebral compression fractures, kyphosis, and leg length discrepancy when it is not recognized early or treated adequately. The diagnosis of CNO is made by excluding alternatives in the differential diagnosis including malignancy (leukemia, lymphoma, and primary or metastatic bone tumors), Langerhans cell histiocytosis, and infection. Clinical assessment in conjunction with serum inflammatory parameters and imaging studies, particularly magnetic resonance imaging (MRI), are crucial for the diagnosis and monitoring of disease activity of CNO1.
Because of significant variation in clinical treatment practices among pediatric rheumatologists, standardized treatment regimens (consensus treatment plans, CTPs) have been developed within the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a North American organization comprised of pediatric rheumatologists and researchers, for CNO patients with an NSAID-refractory course and/or with active spinal lesions2. These CTPs provide an opportunity for pediatric rheumatologists to conduct comparative effectiveness research on CNO through prospective data collection. CRMO/CNO workgroup is comprised of pediatric rheumatologists from North America as well as international colleagues who are interested in collaborating in CNO research. Furthermore, risk factors of severe disease have been described by Wipff et al. based on a large retrospective cohort study3. Their results may be validated by an independent prospective cohort study. To date, there has been only one prospective study on CNO since its first description in 19724. Therefore, we propose to establish this international registry of patients with CNO to accomplish above goals. Long-term outcomes of CNO remains unknown due to the lack of prospective study. It has been estimated that at least 50% of CNO patients continue to need medications for CNO during adulthood. Our study will collect the clinical data and provide valuable data to characterize the long-term outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Age at enrollment is equal to or younger than 21 years of age
- •Presence of bone edema on STIR or T2 fat saturation sequence on MRI within 12 weeks of enrollment
- •Whole body imaging evaluation (either WB MRI or bone scintigraphy)
- •Bone biopsy to exclude infection or malignancy unless bone lesions follow typical distribution or there is IBD, psoriasis, or palmar plantar pustulosis
排除标准
- •- History of or current malignancy
- •Current infectious osteomyelitis
- •Contraindication to the selected treatment agent
研究组 & 干预措施
disease modifying anti-rheumatic drug, DMARD
- Methotrexate 1 mg/kg (max 25 mg) PO or SQ weekly
- Sulfasalazine 30 mg/kg (max 1000 mg) PO twice daily
- Leflunomide 10-20 mg PO daily
干预措施: Methotrexate (Drug)
disease modifying anti-rheumatic drug, DMARD
- Methotrexate 1 mg/kg (max 25 mg) PO or SQ weekly
- Sulfasalazine 30 mg/kg (max 1000 mg) PO twice daily
- Leflunomide 10-20 mg PO daily
干预措施: Sulfasalazine (Drug)
disease modifying anti-rheumatic drug, DMARD
- Methotrexate 1 mg/kg (max 25 mg) PO or SQ weekly
- Sulfasalazine 30 mg/kg (max 1000 mg) PO twice daily
- Leflunomide 10-20 mg PO daily
干预措施: Leflunomide (Drug)
tumor necrosis factor inhibitor, TNFi
- Adalimumab (subcutaneous) 10-40 mg SQ every other week
- Etanercept (subcutaneous) 12.5-50 mg SQ every week
- Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks
- Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
干预措施: Etanercept (Drug)
tumor necrosis factor inhibitor, TNFi
- Adalimumab (subcutaneous) 10-40 mg SQ every other week
- Etanercept (subcutaneous) 12.5-50 mg SQ every week
- Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks
- Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
干预措施: Adalimumab (Drug)
tumor necrosis factor inhibitor, TNFi
- Adalimumab (subcutaneous) 10-40 mg SQ every other week
- Etanercept (subcutaneous) 12.5-50 mg SQ every week
- Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks
- Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
干预措施: Certolizumab (Drug)
tumor necrosis factor inhibitor, TNFi
- Adalimumab (subcutaneous) 10-40 mg SQ every other week
- Etanercept (subcutaneous) 12.5-50 mg SQ every week
- Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks
- Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
干预措施: Infliximab (Drug)
tumor necrosis factor inhibitor, TNFi
- Adalimumab (subcutaneous) 10-40 mg SQ every other week
- Etanercept (subcutaneous) 12.5-50 mg SQ every week
- Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks
- Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
干预措施: Golimumab (Drug)
bisphosphonate
- Pamidronate 1 mg/kg (max 90 mg) (intravenous)*:
Option 1: every month Option 2: 3 consecutive days every 3 months 2. Zoledronic acid 0.0125-0.05 mg/kg (max 4mg) (intravenous): every 3-6 months. * Both options may use lower dose of 0.5 mg/kg at the initiation of the treatment. All options allow concurrent use of NSAIDs.
干预措施: Pamidronate (Drug)
bisphosphonate
- Pamidronate 1 mg/kg (max 90 mg) (intravenous)*:
Option 1: every month Option 2: 3 consecutive days every 3 months 2. Zoledronic acid 0.0125-0.05 mg/kg (max 4mg) (intravenous): every 3-6 months. * Both options may use lower dose of 0.5 mg/kg at the initiation of the treatment. All options allow concurrent use of NSAIDs.
干预措施: Zoledronic acid (Drug)
non-steroidal anti-inflammatory drugs
- Naproxen 10 mg/kg (max 500 mg) PO twice daily
- Indomethacin 1 mg/kg (max daily dose 150 mg) PO twice or three times daily
- Meloxicam 0.1-0.3 mg/kg (max 15 mg) PO daily
- Piroxicam 10-20 mg PO daily
- Ibuprofen 10 mg/kg (max 800 mg) PO 3-4 times daily
干预措施: NSAID (Drug)
结局指标
主要结局
The change of CNO disease activity score
时间窗: 3-6 months
Disease activity score is calculated as the sum of number of clinical lesion count, patient global assessment (0-10), physician global assessment (0-10)
次要结局
- Safety monitoring(5 years)
- Total number of CNO lesions on MRI(3-6 months)
研究者
Yongdong (Dan) Zhao
Principle Investigator
Seattle Children's Hospital