Predicting Dupilumab Treatment Outcome in Patients with Primary diffuse Type 2 Chronic Rhinosinusitis

Background: Chronic rhinosinusitis with a type 2 inflammatory pattern (T2CRS) is believed to be restricted to the nose & sinuses and associated with polyps, without clear serologic markers. Dupilumab is a promising new therapy in difficult to treat T2CRS. No factors are known to predict dupilumab treatment outcome. Methods: Patients undergoing dupilumab treatment were assessed clinically to report ultra-short- and short-term outcome up to 90 days. Serum samples were taken on day 0 and 30 days of treatment, and proteomic analyses were performed using Olink®. The results were compared to healthy controls (HC). The aim was to identify clinical and serological markers associated with a treatment response to dupilumab. Confirmation of predictive parameters was evaluated in a prospective cohort of 20 T2CRS patients. Results: 30 patients were included, 80% of which were treatment responders. SinoNasalOutcomeTest-20 (SNOT-20) scores and the total nasal polyp score improved significantly (p<0.05) on day 7. An improvement of 2.5 points at the first visit was associated with a favorable outcome with a sensitivity of 86%. Proteomic analyses revealed significant changes compared to HC. Furthermore, we could identify OPG in the serum of dupilumab treated patients that may serve as a predictor of the clinical outcome of dupilumab treatment. The predictive value of OPG was confirmed in the second cohort. Conclusion: Clinical response after one week of treatment with dupilumab is highly associated with a favorable outcome. High sensitivity proteomic analyses can identify T2CRS specific dysregulated proteins in serum. Serum OPG may serve as a predictor for dupilumab treatment outcome before the initiation of any therapy. Keywords: Anti IL-4/13; CRS; eosinophilia; predictor; proteomics