Efficacy of second-line therapeutic strategies in patients with chronic nonbacterial osteomyelitis refractory to NSAIDs: A systematic review.
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OBJECTIVE: To evaluate the efficacy and safety of second-line therapies in pediatric patients with chronic nonbacterial osteomyelitis (CNO) that responded poorly to nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: A systematic review of observational studies, cohort studies, and case series (n = 13) involving patients aged less than 15 years with a diagnosis of CNO. We analyzed clinical and radiological remission rates, safety profiles, and the incidence of adverse events for the different therapeutic regimens. RESULTS: The efficacy of NSAIDs in monotherapy was limited (18%-57%). Among second-line therapies, bisphosphonates (particularly pamidronate) and tumor necrosis factor-α inhibitors (TNF inhibitors) achieved the highest response rates, with remission levels between 70% and 91%. Pamidronate proved highly effective for spinal lesions, achieving rapid pain resolution. TNF inhibitors were particularly effective in refractory cases and for the prevention of long-term relapses. The efficacy of disease-modifying antirheumatic drugs (DMARDs) was lower and inconsistent (12%-50%). No serious adverse effects were reported; the most frequent event was flu-like syndrome following the first pamidronate infusion. CONCLUSIONS: Bisphosphonates and TNF inhibitors constitute the most effective and safe second-line strategies for the treatment of refractory CNO. Early diagnosis and appropriate therapeutic scaling are essential to achieve complete remission and prevent permanent bone sequelae, such as spinal fractures or deformities.