Evaluating Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Using Real-World Data

Abstract

Highlights What are the main findings? • Tumor necrosis factor (TNF) inhibitors were the most frequently used treatment strategy in patients with more severe chronic nonbacterial osteomyelitis (CNO), particularly those with spinal involvement or a higher magnetic resonance imaging (MRI) lesion burden, and achieved the highest remission rate.• The Chronic Nonbacterial Osteomyelitis Clinical Disease Activity Score (CNO-CDAS) markedly decreased during follow-up, with most patients achieving either medicated or drug-free remission at the final visit. What are the implications of the main findings? • In this multicenter retrospective cohort of 171 children with chronic nonbacterial osteomyelitis followed for a median of 36 months, disease activity significantly improved, and 91.2% achieved remission at the last visit.• Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans provide a useful framework for real-world treatment decisions in pediatric CNO, particularly for patients with refractory or severe disease.• CNO-CDAS appears to be a practical clinical tool for monitoring disease activity and treatment response and may be integrated into routine clinical practice. Abstract Introduction: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder. To standardize management, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed three consensus treatment plans (CTPs) (1: methotrexate or sulfasalazine [conventional disease-modifying antirheumatic drugs; DMARDs], 2: tumor necrosis factor (TNF)-alpha inhibitors (TNFi), and 3: bisphosphonates). The Clinical Disease Activity Score (CNO CDAS) was introduced to assess disease activity without relying solely on imaging. Objective: The objectives were to evaluate clinicians’ tendencies in applying CNO-CTPs and to assess treatment responses using CNO CDAS in real-world practice, including therapeutic strategies and outcomes at final follow-up. Methods: A retrospective cohort study of 171 pediatric patients with CNO from 18 centers was conducted. Disease activity was assessed using CDAS at diagnosis, at treatment modification, and at the last visit. This score incorporates clinically active lesions, patient pain, and global assessment. Treatments included NSAIDs, DMARDs, TNFi, and pamidronate. Results: Median age was 10 years at onset and 14 years at last follow-up, with a median follow-up of 36 months. The most frequent symptoms were bone pain (95.3%), activity limitation (67.8%), and fatigue (35.1%). All patients received NSAIDs; methotrexate (85.4%) and TNFi (54.4%) were commonly used. TNF inhibitors were the most used CTP, especially in patients with spinal involvement or higher MRI lesion counts, and they achieved the highest remission rate (40.4%). Of the 89 (52.0%) patients who changed treatment, 93.2% switched from DMARDs to TNFi. At the final follow-up, 62% were in medicated remission, 29.2% were in unmedicated remission, and 8.8% had active disease. CDAS scores significantly improved over time (p < 0.05). Conclusions: CARRA CTPs are effective in clinical practice, with anti-TNF therapy yielding the highest remission rates and marked improvement in CDAS.