CHronic Nonbacterial Osteomyelitis International Registry

Official title

CHronic Nonbacterial Osteomyelitis International Registry (CHOIR)

Overview

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.

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.

Interventions

• 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
• Drug Leflunomide
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Pamidronate
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Zoledronic acid
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Etanercept
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Adalimumab
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Certolizumab
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Infliximab
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs
• Drug Golimumab
  second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Primary outcome measures

• The change of CNO disease activity score [Time frame: 3-6 months]

Secondary outcome measures (2)

• Total number of CNO lesions on MRI [Time frame: 3-6 months]
• Safety monitoring [Time frame: 5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Seattle Children's Hospital — Seattle

Publications

• Zhao Y, Wu EY, Oliver MS, Cooper AM, Basiaga ML, Vora SS, Lee TC, Fox E, Amarilyo G, Stern SM, Dvergsten JA, Haines KA, Rouster-Stevens KA, Onel KB, Cherian J, Hausmann JS, Miettunen P, Cellucci T, Nuruzzaman F, Taneja A, Barron KS, Hollander MC, Lapidus SK, Li SC, Ozen S, Girschick H, Laxer RM, Dedeoglu F, Hedrich CM, Ferguson PJ; Chronic Nonbacterial Osteomyelitis/Chronic Recurrent Multifocal Os PMID 29112802
• Zhao Y, Ferguson PJ. Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis in Children. Pediatr Clin North Am. 2018 Aug;65(4):783-800. doi: 10.1016/j.pcl.2018.04.003. PMID 30031498
• Oliver M, Lee TC, Halpern-Felsher B, Murray E, Schwartz R, Zhao Y; CARRA SVARD CRMO/CNO workgroup. Disease burden and social impact of pediatric chronic nonbacterial osteomyelitis from the patient and family perspective. Pediatr Rheumatol Online J. 2018 Dec 14;16(1):78. doi: 10.1186/s12969-018-0294-1. PMID 30547806
• Beck C, Morbach H, Beer M, Stenzel M, Tappe D, Gattenlohner S, Hofmann U, Raab P, Girschick HJ. Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther. 2010;12(2):R74. doi: 10.1186/ar2992. PMID 20433730
• Girschick H, Finetti M, Orlando F, Schalm S, Insalaco A, Ganser G, Nielsen S, Herlin T, Kone-Paut I, Martino S, Cattalini M, Anton J, Mohammed Al-Mayouf S, Hofer M, Quartier P, Boros C, Kuemmerle-Deschner J, Pires Marafon D, Alessio M, Schwarz T, Ruperto N, Martini A, Jansson A, Gattorno M; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever registry. The multiface PMID 29596638
• Voit AM, Arnoldi AP, Douis H, Bleisteiner F, Jansson MK, Reiser MF, Weckbach S, Jansson AF. Whole-body Magnetic Resonance Imaging in Chronic Recurrent Multifocal Osteomyelitis: Clinical Longterm Assessment May Underestimate Activity. J Rheumatol. 2015 Aug;42(8):1455-62. doi: 10.3899/jrheum.141026. Epub 2015 May 15. PMID 25979713
• Wu EY, Oliver M, Scheck J, Lapidus S, Akca UK, Yasin S, Stern SM, Insalaco A, Pardeo M, Simonini G, Marrani E, Wang X, Huang B, Kovalick LK, Rosenwasser N, Casselman G, Liau A, Shao Y, Yang C, Mosa DM, Tucker L, Girschick H, Laxer RM, Akikusa JD, Hedrich CM, Onel K, Dedeoglu F, Twilt M, Ferguson PJ, Ozen S, Zhao Y. Feasibility of Conducting Comparative Effectiveness Research and Validation of a Cl PMID 37399459

Identifiers

NCT: NCT04725422 · 1232

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗