One-year evaluation of canakinumab's safety and efficacy in Japanese patients with Schnitzler syndrome alongside a parallel exploratory analysis

Summary: Abstract Body: Schnitzler syndrome (SchS) is characterized by an urticaria-like rash and monoclonal gammopathy, frequently accompanied by fever and fatigue. No approved treatment currently exists, and its pathogenesis remains unclear. We conducted a multicenter, single-arm, open-label phase II trial to assess canakinumab's safety and efficacy in Japanese SchS patients, based on prior German studies. Previously, we reported results up to 24 weeks; here, we extend findings to 48 weeks, including exploratory analyses. Five active cases with no prior IL-1-targeted treatment were enrolled. scRNA sequencing and spatial transcriptomics identified IL1B-expressing cells in two cases. Canakinumab, given every 8 weeks, continued improving symptoms, lab abnormalities, and quality of life up to 48 weeks, with no new adverse events. Dynamic Time Warping analysis evaluated variations in 32 cytokines/chemokines, 11 complement factors, and clinical symptoms through subjective measures and blood tests. Symptoms correlated strongly with WBC count, neutrophil count, CRP, and SAA levels, while IL-1β and most cytokines/chemokines showed distinct patterns. IgM levels differed from symptom patterns. Although monocytes and mast cells were thought to be primary IL1B-expressing cells, we found neutrophils were predominant in both blood and skin. Notably, blood neutrophil counts decreased post-canakinumab. Thus, canakinumab, targeting IL-1β, showed sustained efficacy and safety in Japanese SchS patients over 48 weeks, suggesting its potential to control peripheral blood neutrophils in SchS treatment. Naotomo Kambe¹, Satoshi Nakamizo¹, Norimitsu Inoue², Nobuo Kanazawa³ 1. Dermatology, Kyoto University, Kyoto, Japan. 2. Molecular Genetics, Wakayama Medical University, Wakayama, Japan. 3. Dermatology, Hyogo Medical University, Nishinomiya, Japan. Clinical Research: Interventional Research