Effective Treatment of Janus Kinase 1/3 Inhibitor in Blau Syndrome From a Multicenter Retrospective Study in Central China.

OBJECTIVE: We sought to investigate the effectiveness of the Janus kinase 1/3 inhibitor (JAK1/3i) tofacitinib (TOF) in treating Blau syndrome (BS), and to explore the association between various clinical and genetic features and therapeutic responses within the cohort.

METHODS: A 5-year, multicenter, retrospective, observational study (ClinicalTrials.gov: NCT06688838) was conducted across 7 centers, focusing on genetic profiles and the clinical manifestations of the cohort. Genetic analysis, including whole-exome sequencing and nucleotide-binding oligomerization domain 2 (NOD2) and signal transducer and activator of transcription 3 (STAT3) rs2293152 phenotypic comparisons, was performed to assess therapeutic responses.

RESULTS: All patients had arthritis, with 2 cases being oligoarticular and 22 polyarticular. The joints primarily affected included the wrists, proximal interphalangeal joints, ankles, and knees. Radiographic analysis revealed symmetrical nonerosive arthropathy in 92.3% of patients. Notably, two-thirds of the cohort displayed previously unrecognized dysplastic bone changes. Ocular involvement was observed in all patients. Notably, no association was found between different NOD2 sequences and therapy response. Conversely, patients harboring the STAT3 rs2293152 GG polymorphism demonstrated favorable responses to treatment, regardless of whether JAK1/3i or tumor necrosis factor inhibitors (TNFi) were used.

CONCLUSION: TOF could be an effective therapeutic option for patients with BS who demonstrate resistance to TNFi or corticosteroids. Specifically, the STAT3 rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.