CHronic Nonbacterial Osteomyelitis International Registry (CHOIR)

Study Overview
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Brief Summary
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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 5 years.

Official Title
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CHronic Nonbacterial Osteomyelitis International Registry (CHOIR)

Conditions
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Chronic Nonbacterial Osteomyelitis, Chronic Recurrent Multifocal Osteomyelitis

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Sulfasalazine
* Drug: Leflunomide
* Drug: Pamidronate
* Drug: Zoledronic acid
* Drug: Etanercept
* Drug: Adalimumab
* Drug: Certolizumab
* Drug: Infliximab
* Drug: Golimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| disease modifying anti-rheumatic drug, DMARD<br> | Drug: Methotrexate<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Sulfasalazine<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Leflunomide<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>|
| tumor necrosis factor inhibitor, TNFi<br> | Drug: Etanercept<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Adalimumab<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Certolizumab<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Infliximab<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Golimumab<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>|
| bisphosphonate<br> | Drug: Pamidronate<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>Drug: Zoledronic acid<br>* second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of CNO disease activity score | Disease activity score is calculated as the sum of number of clinical lesion count, patient global assessment (0-10), physician global assessment (0-10) | 3-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of CNO lesions on MRI | The total number of CNO lesions from MRI as previously described (Zhao, et al. J Rheum 2019) will be used to monitor response in a subset | 3-6 months | 
| Safety monitoring | Serious adverse events including infections that require IV antibiotics, malignancy, hematological, hepatic, dermatological side effects will be reported | 5 years |