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

Allergy. 2023 Apr;78(4):1036-1046. doi: 10.1111/all.15532. Epub 2022 Oct 10.

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.

Keywords: anti IL-4/13; chronic rhinosinusitis; eosinophilia; predictor; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Humans
  • Nasal Polyps* / complications
  • Nasal Polyps* / drug therapy
  • Prospective Studies
  • Proteomics
  • Rhinitis* / complications
  • Rhinitis* / drug therapy
  • Sinusitis* / complications
  • Sinusitis* / drug therapy
  • Treatment Outcome

Substances

  • dupilumab