Predicting dupilumab treatment outcome in patients with primary diffuse type 2 chronic rhinosinusitis

Abstract Background Chronic rhinosinusitis with a type 2 inflammatory pattern (T2CRS) is believed to be restricted to the nose and 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 with 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 Thirty patients were included, 80% of which were treatment responders. SinoNasalOutcomeTest‐20 (SNOT‐20) scores and the total nasal polyp score improved significantly ( p < .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 with 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 1 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.