Clinical and transcriptional response to the long‐acting interleukin‐1 blocker canakinumab in Blau syndrome–related uveitis

Abstract

Objective To report on the clinical response to canakinumab in a patient with sporadic nucleotide-binding oligomerization domain–containing protein 2 (NOD-2)–associated pediatric granulomatous arthritis (Blau syndrome) and severe resistant panuveitis, and to describe gene expression profile changes throughout such treatment. Methods A 4-year-old boy was diagnosed as having Blau syndrome on the basis of typical clinical features, histologic evidence of noncaseating granulomas, and a NOD2 mutation. Ocular involvement was initially controlled by topical and oral corticosteroids, but over the years visual impairment and complications, such as macular edema and retinal detachment, progressed. Ocular disease remained persistently active despite treatment with multiple different immunosuppressants; therefore, canakinumab treatment was started. Before and during the first 6 months of treatment, the gene expression profile was determined each month. Results Canakinumab treatment was well tolerated and led to rapid quiescence of uveitis, which had been continuously active before this treatment. Gene expression profiling analysis of the patient's blood prior to initiation of interleukin-1 (IL-1) blockade revealed differential expression of 1,993 transcripts when compared to healthy controls, and among the up-regulated transcripts, pathway analysis showed that the predominant network consisted of innate immunity–related transcripts. The transcriptional signature of the patient overlapped with the transcriptional signature of patients with systemic-onset juvenile idiopathic arthritis, and canakinumab treatment led to the normalization of most of these transcriptional changes. Conclusion The pathogenesis of Blau syndrome may be mediated by IL-1, and canakinumab may be useful when this disorder is unresponsive to more conventional treatments.

Diagnosis and Treatment of Blau Syndrome/Early-onset Sarcoidosis, an Autoinflammatory Granulomatous Disease, in an Infant

“…Interleukin (IL)-1β receptor antagonist, such as anakinra and canakinumab, have been used with variable clinical outcome (3,12). In cases with severe uveitis canakinumab may be useful (12). In our case infliximab in combination with MTX induced remission for 8 months.…”

“…Also, TNF-α inhibitors, such as infliximab and adalimumab, are used in BS/EOS (10,11). Interleukin (IL)-1β receptor antagonist, such as anakinra and canakinumab, have been used with variable clinical outcome (3,12). In cases with severe uveitis canakinumab may be useful (12).…”

Canakinumab for Childhood Sight-threatening Refractory Uveitis: A Case Series

“…It has been successfully used in cryopyrin-associated periodic syndromes 3 , systemic-onset juvenile idiopathic arthritis (JIA) 4 , refractory Behçet disease 5,6 , and colchicine-resistant familial Mediterranean fever 7 . Preliminary evidences suggest the efficacy of canakinumab for refractory eye diseases in patients affected by Blau syndrome 8 , juvenile Behçet syndrome 9 , and chronic infantile neurologic cutaneous and articular syndrome 10 . Here we report 2 children affected by refractory sight-threatening uveitis who have been successfully treated with canakinumab.…”

Autoinflammatorische Syndrome im Kindesalter

“…Die Sympto me scheinen gut auf eine Steroidtherapie anzusprechen, refraktäre Fälle können mit Anakinra oder TNFInhibitoren behandelt werden [25].…”