CT Mucus Score and 129Xe MRI Ventilation Defects after 2.5-years anti-IL-5Rα in Eosinophilic Asthma.

BACKGROUND: We previously showed in poorly controlled eosinophilic asthma patients that a single dose of benralizumab resulted in significantly improved asthma-control-questionnaire (ACQ-6) score and 129 Xe magnetic-resonance-imaging (MRI) ventilation defect percent (VDP), 28-days post-injection, and 129 Xe MRI VDP and computed tomography (CT) airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab.

RESEARCH QUESTION: Do early VDP responses at 28-days persist and do FEV1 , FeNO and mucus-plug score improve during a 2.5-year treatment period?

STUDY DESIGN AND METHODS: Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6 and MRI, 28-days, 1- and 2.5-years post-benralizumab; chest CT was acquired at enrollment and 2.5-years later.

RESULTS: Of 29 participants evaluated at 28-days post-benralizumab, 16 participants returned for follow-up whilst on therapy at 1-year and 13 participants were evaluable whilst on therapy at 2.5-years, post-benralizumab initiation. As compared to 28-days post-benralizumab, ACQ-6 score (2.0±1.4) significantly improved after 1-year (0.5±0.6, p=.02; 95% confidence interval [CI], 0.1-1.1) and 2.5-years (0.5±0.5, p=.03; 95% CI, 0.1-1.1). The mean VDP change at 2.5-years (-4±3%) was greater than the minimal-clinically-important-difference, but not significantly different than VDP measured 28-days post-benralizumab. Mucus-score (3±4) was significantly improved at 2.5-years (1±1, p=.03; 95% CI, 0.3-5.5). In six of eight participants with previous occlusions, mucus-plugs vanished or substantially diminished 2.5-years later. VDP (p<.001) and mucus-score (p<.001) measured at baseline, but not FeNO or FEV1 , independently predicted ACQ-score after 2.5-years.

INTERPRETATION: In poorly controlled eosinophilic asthma, early MRI VDP responses at 28-days post-benralizumab persisted 2.5-years later, alongside significantly improved mucus-score and asthma-control.