Real-world efficacy of stapokibart for severe olfactory dysfunction: early and sustained improvement independent of baseline type 2 inflammation status and nasal polyp burden

Background Olfactory dysfunction (OD) is a key feature of chronic rhinosinusitis with nasal polyps (CRSwNP), resulting from both mechanical obstruction and sensorineural injury. Stapokibart is a humanized anti-IL-4 receptor alpha antibody, and this real-world study aimed to evaluate its efficacy in CRSwNP patients with moderate-to-severe OD, as well as the impact of baseline characteristics on olfactory recovery. Methods A total of 40 CRSwNP patients with moderate-to-severe OD were enrolled. All patients received subcutaneous stapokibart at a dose of 300 mg every 2 weeks for 16 weeks. Subjective olfactory outcome (smell loss VAS) and objective olfactory outcome (SSIT-16) were assessed at Weeks 0, 2, 4, 8, and 16. Subgroup analyses were stratified by baseline inflammatory markers and prior surgery history. Results Stapokibart led to rapid and sustained olfactory improvement: smell loss VAS was significantly reduced by Week 2 (P<0.0001). At Week 16, 52.5% of patients achieved normosmia, with the mean objective olfactory score increasing from 3.05 ± 2.98 to 11.35 ± 3.73 (P<0.0001) and nasal polyp score decreasing from 4.03 ± 1.70 to 1.63 ± 1.61 (P<0.001). Olfactory recovery was consistent across subgroups, regardless of baseline IgE level, eosinophil count, or previous sinus surgery. Patients with higher baseline polyp burden showed faster early improvement but similar final outcomes. Conclusion Stapokibart effectively and rapidly improves olfactory function in CRSwNP. Baseline nasal polyp burden affects the speed but not the magnitude of recovery, supporting the clinical utility of stapokibart in patients with moderate-to-severe OD.