The place of JAK inhibitors in systemic juvenile idiopathic arthritis with lung disease (SJIA-LD): French experience

Abstract Objectives A new form of systemic juvenile idiopathic arthritis (SJIA) with associated lung disease (SJIA-LD) has recently been described. Multiple lines of treatment have failed to yield satisfactory results for this disorder. Janus kinase inhibitors (JAKis) have recently been approved for the treatment of JIA, but clinical evidence of their efficacy in SJIA-LD is still weak. Here we describe and assess real-life experience of SJIA-LD treatment with JAKis in France. Methods This is a retrospective study based on information gathered from patients’ medical records. Systemic and pulmonary symptoms and biological data including CRP, ferritin, IL-18, chest CT scan and functional respiratory tests were collected. Results Eight patients with SJIA-LD were identified in French paediatric rheumatology centres. All received at least one JAKi (baricitinib, ruxolitinib and/or tofacitinib). Complete disease control was obtained in four patients. Steroids were tapered in four patients and stopped in two. Three patients presented an episode of macrophage activation syndrome (MAS) shortly after anti-IL-1s were stopped when JAKis were introduced. Two patients had other serious side effects (viral reactivation—EBV, BK virus, cytopenia). At last follow-up, one patient had died from severe MAS, two patients had undergone haematopoietic stem cell transplantation, four were in complete response (two of them free of steroids), and one in partial response with JAKis. Lung response to JAKi was not clearly linked to disease duration. Conclusion JAKis offer another therapeutic option for patients with SJIA-LD. However, the risk of MAS argues for caution about stopping anti-IL-1s when introducing JAKis. Tolerance needs careful monitoring in larger studies..