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

Abstract

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. 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 <i>nucleotide-binding oligomerization domain 2</i> (<i>NOD2</i>) and <i>signal transducer and activator of transcription 3</i> (<i>STAT3)</i> rs2293152 phenotypic comparisons, was performed to assess therapeutic responses. 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 <i>NOD2</i> sequences and therapy response. Conversely, patients harboring the <i>STAT3</i> rs2293152 GG polymorphism demonstrated favorable responses to treatment, regardless of whether JAK1/3i or tumor necrosis factor inhibitors (TNFi) were used. TOF could be an effective therapeutic option for patients with BS who demonstrate resistance to TNFi or corticosteroids. Specifically, the <i>STAT3</i> rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.