Effective treatment of Jak1/3 inhibitor in Blau syndrome from a multi-center retrospective study in central China

Objective To investigate the effectiveness of the JAK 1/3 inhibitor tofacitinib in treating Blau syndrome and explore the association between various clinical and genetic features and therapeutic responses within the cohort. Methods A five-year, multi-center, retrospective, observational study was conducted across seven centers, focusing on genetic profiles and the clinical manifestations of cohort. Genetic analysis, including whole exome sequencing and NOD-2 and STAT3 rs2293152 phenotypic comparisons, was performed to assess therapeutic responses. Results Baseline data for the cohort, with a median disease duration of 9.3 years. All patients exhibited arthritis, with 2 cases being oligoarticular and 22 polyarticular. The median joint count involved was 6, primarily affecting wrists, proximal interphalangeal joints, ankles, and knees. Radiographic analysis revealed symmetrical non-erosive 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 NOD-2 sequences and therapy response. Conversely, patients harboring the STAT3 rs2293152 GG polymorphism demonstrated favorable responses treatment, regardless of whether JAK1/3 inhibitors or TNF-α inhibitors were used. Conclusion Tofacitinib could be an effective therapeutic option for BS patients who demonstrate resistance to TNF-α inhibitors or corticosteroids. Specifically, the STAT3 rs2293152 GG polymorphism was associated with improved response to treatment, suggesting a genotype-influenced therapeutic efficacy.