Stapokibart efficacy by asthma status in chronic rhinosinusitis with nasal polyps: a post hoc analysis of the CROWNS-2 trial

Background: Asthma is a common comorbidity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Stapokibart, a novel anti-interleukin-4 receptor alpha monoclonal antibody, demonstrated efficacy and safety in patients with CRSwNP in a phase 3 trial (NCT05436275). Objective: To evaluate stapokibart’s efficacy and safety in patients with CRSwNP with/without comorbid asthma. Methods: Patients were randomized (1:1) to subcutaneous stapokibart 300 mg or placebo Q2W for 24 weeks. Post-hoc subgroup analyses (with/without comorbid asthma) assessed changes from baseline in nasal polyp score (NPS), nasal congestion score (NCS), Lund–Mackay computed tomography (CT) score, total symptom score (TSS), loss-of-smell score, 22-item Sino-nasal Outcome Test (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, along with NPS and NCS response rates. Results: Of 179 patients, 89 (49.7%) had comorbid asthma. At week 24, stapokibart significantly improved NPS, NCS, Lund–Mackay CT score, UPSIT score, loss-of-smell score, TSS, and SNOT-22 score compared with placebo, irrespective of asthma status (all P < 0.01). Patients with comorbid asthma demonstrated greater improvements in TSS, olfactory function, and Lund–Mackay CT score at week 24 compared with those without comorbid asthma (all interaction P < 0.05). In the asthma subgroup, stapokibart increased the proportions of patients achieving ≥1- and ≥2-point reductions in NPS and ≥0.5- and ≥1-point reductions in NCS versus placebo (all P < 0.0001); among patients without asthma, similar trends were observed, although NCS response rates improvements did not reach statistical significance ( P = 0.086 and P = 0.052, respectively). The safety profile was similar across groups. Conclusion: Stapokibart improved NPS, NCS, Lund–Mackay CT score, UPSIT score, loss-of-smell score, TSS, and SNOT-22 score regardless of asthma status. Exploratory interaction analyses suggested potentially greater improvements in TSS, olfactory outcomes, and sinus opacification in patients with comorbid asthma.