Efficacy of Dupilumab for Patients with Chronic Rhinosinusitis without Nasal Polyps: a Randomized Double-Blind Placebo Controlled Phase II Study.

Background

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a heterogeneous inflammatory disease affecting up to 8% of the population. No biologic therapies are currently approved for CRSsNP, and emerging data suggest that T2-high endotypes may respond preferentially to targeted therapy.

Objective

To evaluate the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin-4/interleukin-13 signaling pathway, in patients with moderate-severe CRSsNP and to explore differential responses by T2-inflammatory endotype.

Methods

In a 6-month, randomized, double-blind, placebo-controlled trial, 33 adults with moderate-severe CRSsNP received dupilumab 300 mg or placebo every 2 weeks. Primary outcomes were change in 22-item Sino-Nasal Outcome Test (SNOT-22) and mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ) scores. Secondary outcomes included CT sinus scores and use of rescue medications. Prespecified subgroup analyses were performed in T2-high patients, defined by pronounced allergen skin test positivity or elevated blood eosinophils.

Results

Dupilumab significantly improved SNOT-22 (-7.0 vs placebo; P<.001) and mini-RQLQ (-5.2 vs placebo; P<.01) scores. T2-high patients showed numerically greater improvement in SNOT-22 (-11.3; P=.07) and significant improvement in mini-RQLQ (-9.2; P<.01). Reductions in CT scores and rescue medication use favored dupilumab but were not statistically significant. Treatment was well tolerated, and all participants completed the study.

Conclusion

Dupilumab was associated with meaningful improvements in patient-reported outcomes in adults with CRSsNP. The observed trend toward enhanced benefit in T2-high patients supports the potential for endotype-directed therapy and underscores the need for larger studies to evaluate the role of T2-targeted biologics in CRSsNP management.