Review of ruxolitinib for systemic juvenile arthritis with macrophage activation syndrome

ObjectiveTo explore the efficacy and safety of ruxolitinib in children with systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome (sJIA-MAS), particularly in those with refractory disease.MethodsThe clinical courses of two children with refractory sJIA-MAS treated with ruxolitinib at our center were retrospectively reviewed. In addition, Chinese and English databases were searched to summarize the clinical features, therapeutic outcomes, and safety of ruxolitinib in pediatric sJIA-MAS.ResultsIn both patients from our center, systemic hyperinflammation improved markedly during combined therapy that included ruxolitinib, allowing glucocorticoids to be gradually tapered and discontinued without relapse. Case 1 was a 19-month-old boy diagnosed with refractory sJIA-MAS complicated by respiratory failure. Despite methylprednisolone pulse therapy, low-grade fever and rash persisted. After starting ruxolitinib, body temperature stabilized and clinical symptoms improved rapidly. Glucocorticoids were discontinued within three months, and tocilizumab was stopped after one year. Case 2 was a 4-year-old girl diagnosed with refractory sJIA-MAS complicated by acute respiratory distress syndrome and thrombocytopenia. She received methylprednisolone pulse therapy and ruxolitinib combined with plasma exchange (three sessions). Body temperature normalized on the second day after ruxolitinib initiation. Dyspnea resolved, and ferritin levels normalized within 10 days. Glucocorticoids were discontinued within six months. No ruxolitinib-related adverse events were observed. In addition, five previously reported pediatric cases were identified. A total of seven children (three males and four females; age range 1–11 years) were analyzed. Of the seven patients reviewed, five met criteria for refractory sJIA-MAS, while two were not strictly refractory but received ruxolitinib due to incomplete response or intolerance to standard therapy. Five achieved complete remission and two achieved partial remission. Two patients experienced relapse during glucocorticoid tapering and achieved complete remission after the addition of canakinumab. No deaths were reported. One patient developed Epstein–Barr virus–associated hemophagocytic lymphohistiocytosis and neutropenia after ruxolitinib treatment, which resolved after drug discontinuation and plasma exchange.ConclusionRuxolitinib may serve as a potential rescue or bridging therapy for patients with sJIA-MAS, especially those with refractory disease unresponsive to first-line therapy. Close monitoring for cytopenia and viral infections is recommended during treatment.