1245 Zhao, et al: Aggressive therapy reduces CNO Personal non-commercial use only. The Journal of Rheumatology Copyright © 2015. All rights reserved. Aggressive Therapy Reduces Disease Activity without Skeletal Damage Progression in Chronic Nonbacterial Osteomyelitis Yongdong Zhao, Nancy A. Chauvin, Diego Jaramillo, and Jon M. Burnham ABSTRACT. Objective. To retrospectively assess changes in disease activity and skeletal damage in children with chronic nonbacterial osteomyelitis (CNO) after infliximab and methotrexate, with or without zoledronic acid or nonsteroidal antiinflammatory drug (NSAID) monotherapy, using a standardized magnetic resonance imaging (MRI) approach. Methods. Treatment-related changes in clinical and MRI measures from aggressive therapy and NSAID monotherapy groups (n = 9 per group) were evaluated using nonparametric methods. Results. Pain, physical function, physician global assessment, inflammatory markers, nonvertebral inflammatory lesion number, and maximum bone edema score all improved significantly with aggressive therapy (p < 0.03), whereas only the maximum soft tissue inflammation severity decreased (p = 0.02) with NSAID monotherapy. Vertebral deformities and physeal damage did not worsen in the aggressive therapy group but 1 in the NSAID group had worsening of growth plate damage. Conclusion. An aggressive treatment regimen in CNO improved clinical and imaging measures of disease activity without progression of skeletal damage. (First Release May 15 2015; J Rheumatol 2015;42:1245–51; doi:10.3899/jrheum.141138) Key Indexing Terms: CHRONIC NONBACTERIAL OSTEOMYELITIS METHOTREXATE NONSTEROIDAL ANTIINFLAMMATORY DRUGS ZOLEDRONIC ACID MAGNETIC RESONANCE IMAGING INFLIXIMAB From the Pediatric Rheumatology Department, Seattle Children’s Hospital, Seattle, Washington; Department of Radiology, and the Division of Pediatric Rheumatology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. Y. Zhao, MD, PhD, acting assistant professor, Pediatric Rheumatology Department, Seattle Children’s Hospital; N.A. Chauvin, MD, Assistant Professor; D. Jaramillo, MD, MPH, Professor, Department of Radiology, The Children’s Hospital of Philadelphia; J.M. Burnham, MD, MSCE, Associate Professor, Division of Pediatric Rheumatology, The Children’s Hospital of Philadelphia. Address correspondence to Pediatric Rheumatology, The Children’s Hospital of Philadelphia, 3501 Civic Center Blvd., Philadelphia, Pennsylvania 19104, USA. E-mail: burnhams@email.chop.edu Accepted for publication March 17, 2015. Chronic nonbacterial osteomyelitis (CNO) is an inflam- matory bone disease that causes skeletal inflammation and pain, and can be complicated by functional impairment, vertebral fractures, and limb length discrepancy. Although treatment with nonsteroidal antiinflammatory drugs (NSAID) relieves pain in some patients 1,2,3,4,5 , those at risk for skeletal deformities or with persistent pain require additional therapy with tumor necrosis factor–α inhibitors (TNFi) 1,3,6,7,8 or bisphosphonates 4,9,10,11,12, 13,14,15,16 . CNO treatment studies have focused on clinical, labora- tory, and radiographic improvements. Magnetic resonance imaging (MRI) is useful to assess active bone and soft tissue edema, periosteal reaction, and hyperostosis, as well as components of skeletal damage, including physeal bony bar formation and vertebral collapse. Previous MRI-based studies have not examined specific lesion characteristics, mainly reporting the change in the number of lesions and qualitative bone marrow enhancement improvement 2,7,8 . In our practice, TNFi therapy is used for patients with active vertebral disease or CNO-related persistent pain despite NSAID or other nonbiologic disease-modifying therapy. Additionally, MRI is performed at diagnosis to identify individuals with vertebral involvement, who are offered a single dose of bisphosphonate therapy with zoledronic acid (ZOL), with maintenance infliximab (IFX) therapy and concomitant methotrexate (MTX). Our retro- spective study aimed to evaluate changes in clinical and MRI characteristics of CNO in children treated with an aggressive therapy including IFX and MTX, with or without ZOL, and those treated with NSAID monotherapy. Our hypothesis was that aggressive therapy would improve pain, physical function, and MRI characteristics of disease activity, and prevent progression of skeletal damage. MATERIALS AND METHODS Participants. Patients treated for CNO in the Division of Rheumatology at The Children’s Hospital of Philadelphia (USA) from 2006–2013 and 2–18 years of age at diagnosis were identified. Two pediatric rheumatologists (YZ and JMB) confirmed the CNO diagnosis if unifocal or multifocal inflam- matory bone lesions were present without evidence of malignancy or infection according to laboratory tests and histologic examination, if performed 1 . Patients were included if regional or whole body MRI (WBMRI) scans contained multiplanar fluid-sensitive sequences and were www.jrheum.org Downloaded on February 18, 2022 from