Purpose

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.

Conditions

Eligibility

Eligible Ages
Under 21 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • - 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

Exclusion Criteria

  • - History of or current malignancy - Current infectious osteomyelitis - Contraindication to the selected treatment agent

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
disease modifying anti-rheumatic drug, DMARD 1. Methotrexate 1 mg/kg (max 25 mg) PO or SQ weekly 2. Sulfasalazine 30 mg/kg (max 1000 mg) PO twice daily 3. Leflunomide 10-20 mg PO daily
  • Drug: Methotrexate
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
  • Drug: Sulfasalazine
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • Azulfidine
  • Drug: Leflunomide
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • areva
tumor necrosis factor inhibitor, TNFi 1. Adalimumab (subcutaneous) 10-40 mg SQ every other week 2. Etanercept (subcutaneous) 12.5-50 mg SQ every week 3. Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks 4. Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks
  • Drug: Etanercept
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • enbrel
  • Drug: Adalimumab
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • humira
  • Drug: Certolizumab
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • cimzia
  • Drug: Infliximab
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • remicade, inflectra
  • Drug: Golimumab
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • simponi
bisphosphonate 1. 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.
  • Drug: Pamidronate
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
    Other names:
    • Aredia
  • Drug: Zoledronic acid
    second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
non-steroidal anti-inflammatory drugs 1. Naproxen 10 mg/kg (max 500 mg) PO twice daily 2. Indomethacin 1 mg/kg (max daily dose 150 mg) PO twice or three times daily 3. Meloxicam 0.1-0.3 mg/kg (max 15 mg) PO daily 4. Piroxicam 10-20 mg PO daily 5. Ibuprofen 10 mg/kg (max 800 mg) PO 3-4 times daily
  • Drug: NSAID
    first-line treatment

Recruiting Locations

Seattle Children's Hospital
Seattle, Washington 98105
Contact:
Joshua Scheck, BS
206-987-2000
crmoresearch@seattlechildrens.org

More Details

Status
Recruiting
Sponsor
Seattle Children's Hospital

Study Contact

Yongdong (Dan) Zhao, MD, PhD
206-987-2000
crmoresearch@seattlechildrens.org

Detailed Description

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.

Notice

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