基于CT的PRM小气道病变与鼻窦评分预测本瑞利珠单抗应答

原文

BACKGROUND: Benralizumab reduces eosinophilia and improves outcomes in most, but not all, patients with asthma. We evaluated whether baseline CT imaging-derived metrics assist in clinical response prognosis after 52 weeks. RESEARCH QUESTION: Are CT imaging-derived measures prognostic of benralizumab response, assessed by exacerbation reduction, lung function, and symptom control at 52 weeks? STUDY DESIGN AND METHODS: This 2-center prospective, open-label study included patients eligible for anti-IL-5α receptor therapy who began benralizumab treatment alongside high-dose background therapy for severe eosinophilic asthma (SEA; > 300/mm3). Baseline variables included CT imaging-derived metrics (parametric response mapping [PRM] small airways disease [SAD] voxels; University of California, San Francisco, mucus plugging; and Lund-Mackay sinus score) and other potential biomarkers (blood eosinophil levels and lung function). The primary outcome was ≥ 50% reduction in exacerbation rates. The secondary outcome was a composite clinical score achieving ≥ 2 of response criteria: ≥ 50% exacerbation reduction, FEV1 increase of > 300 mL, and 5-item Asthma Control Questionnaire score improvement of > 0.5. RESULTS: Of 59 enrolled patients, 47 patients (60% female; median age, 54 years) completed the study with high-quality paired inspiratory and expiratory spirometrically gated CT scans. Forty-two of 47 patients achieved ≥ 50% exacerbation reduction, for which no prognostic factor could be identified. Thirty-five of 47 patients achieved the secondary outcome. Receiver operating characteristic curve analyses indicated that PRM SAD voxels (area under the receiver operating characteristic curve [AUC], 0.693; 95% CI, 0.513-0.873) and sinus score (AUC, 0.714; 95% CI, 0.501-0.928) were robust prognostic factors of responder status, both outperforming blood eosinophil count (AUC, 0.630; 95% CI, 0.428-0.832). INTERPRETATION: Our results show that the CT imaging-derived metrics, PRM SAD voxels, and sinus score were associated with benralizumab response as defined by a composite clinical end point and could be valuable biomarkers for response prognosis in patients with SEA. The high rate of exacerbation reduction limited discrimination of the primary end point. These findings support incorporating CT imaging phenotyping into precision management of SEA and warrant validation in larger cohorts. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03976310; URL: www. CLINICALTRIALS: gov.