Chronic non-bacterial osteomyelitis in children- five-year standardized follow-up of a prospective observational cohort in the pre-biological era

Abstract

Background: This prospective, long-term observational study, initiated in 2002, aimed to characterize clinical and laboratory data, whole body MRI detected lesions, and treatment responses in 37 juvenile patients with chronic non-bacterial osteomyelitis at a time when biological DMARDs were not yet standard therapy. Methods: Patients were assessed at baseline and at 1 (without MRI), 3, 6, 12, 18, 24, 36, 48, 60 months. All patients received naproxen as first-line therapy. Clinical management allowed for escalation to sulfasalazine, pamidronate, and glucocorticoids as needed. Treatment response was evaluated using the pedCNO disease activity score (30/50/70/90% improvement). Further composite numeric disease activity (DA) scores– the CARRA CDAS and a new MRI DAS - were applied. Results: The mean age at disease onset was 10.8 years, with a diagnostic delay of 5.8 months. Naproxen was the initial treatment in all patients. Second-line therapy was initiated in 10 patients due to inadequate improvement in physician global assessment of disease activity, patient-reported overall wellbeing or MRI lesions. Escalated therapies included sulfasalazine (n = 10), bisphosphonates (n = 1), methotrexate (n = 1), and short- (< 4 wks) or long-term oral glucocorticoids (n = 5 and n = 3, respectively). The mean number of clinical lesions decreased from 2.1 to 0.4 at 12 months and reached 0.15 at 60 months. MRI-detected lesions declined from 5.0 to 2.25 at 12 months and to 1.1 at 60 months. Conclusion: Most children experienced favourable long-term outcomes. Clinical improvement occurred more rapidly than radiologic resolution. Patients with insufficient response to NSAIDs should be considered for a treat-to-target approach, including the use of conventional and biologic DMARDs. Trial registration: A trial registration EUDRA CT was not available at the time the study was started. Informed consent was given by all parents.