Clinical features of responders to mepolizumab in eosinophilic chronic rhinosinusitis and the outcomes post treatment cessation

Background: Recent studies have shown that mepolizumab is an effective treatment in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). Defining which patients will benefit from this treatment is essential in guiding its role in the multimodal approach to CRSwNP and eosinophilic chronic rhinosinusitis (eCRS). The aim of this study is to define the clinical and disease features of those patients who report benefit from therapy compared to non-responders. Methods: A prospective phase 2 clinical trial was undertaken with a single-arm of non-blinded patients with open label therapy with mepolizumab (trial registration ID ACTRN12618000113257) from May 2019 to November 2020. Patients underwent treatment with mepolizumab 100 mg 4-weekly for 6 months. Data was collected at baseline and at 4, 8, 12, 16, 20 and 24 weeks of treatment, as well as 4 months post their last mepolizumab dose. Data collected included patient demographics, blood eosinophil count (cells/L), tissue histopathology outcomes [inflammation severity, type, eosinophil density (cell/HPF)], functional outcomes [endoscopic findings, nasal nitric oxide (nNO), fractional exhaled nitric oxide (FeNO)] and patient reported outcome measures [including Sino-Nasal Outcome Test 22-item (SNOT-22), Asthma Control Questionnaire 5-item (ACQ-5), nasal obstruction visual analogue scores (VAS) and nasal function VAS]. Responders were defined as those patients having a ≥1 improvement in a 13-point ordinal overall nasal function score. Results: Twenty patients were assessed (age 47.7±14.5 years and 50% female). All patients had prior sinus surgery (4.1±3.5 years) and all had comorbid asthma. Fourteen patients (70%) were classed as responders to mepolizumab therapy. Responders were associated with higher baseline symptom burden: SNOT-22 (51.3±17.3 vs. 30.7±19.1, P=0.03), ACQ-5 (2.3±1.2 vs. 1.2±0.5, P=0.03) and lower baseline nNO (300.4±169.7 vs. 645.0±318.7 parts per billion, P=0.005). Within 3 months following cessation of mepolizumab, there was a deterioration of clinical outcomes including blood eosinophils, tissue eosinophils, SNOT-22 and ACQ-5. Conclusions: In eCRS, responders were likely to have more severe symptomatic disease at baseline and lower nNO. Cessation of mepolizumab is associated with deterioration of both objective and subjective markers.