Benralizumab Efficacy in Late Non-Responders to Mepolizumab and Variables Associated with Occurrence of Switching: A Real-Word Perspective

Abstract

Overlapping eligibility to different biologics for severe asthma is still challenging, especially when addressing the same target. We aimed to characterize severe eosinophilic asthma patients according to their maintained or reduced response to mepolizumab over time and to explore baseline variables significantly associated with the occurrence of switching to benralizumab. We performed a multicentre retrospective observational study evaluating OCS reduction, exacerbation rate, lung function, exhaled nitric oxide levels (FeNO), Asthma control test (ACT), and blood eosinophil concentrations at baseline and before and after switching occurrence among 43 female and 25 male patients with severe asthma aged 23 to 84 years. Younger age, higher OCS daily dose and lower blood eosinophils at baseline were associated with a significantly higher risk (odds) for switching occurrence. All the patients showed an optimal response to mepolizumab, up to six months. The need for switching, according to the above-mentioned criterion, occurred for 30 out of 68 patients after a median time of 21 months (Q1-Q3: 12-24) from mepolizumab initiation. At the follow-up time-point after the switch (median time: 31 months, Q-Q3: 22-35), all the outcomes substantially improved and no cases of poor clinical response to benralizumab were detected. Although the small sample size and the retrospective design represent major limitations, to our knowledge, our study provides the first real-word focus on clinical variables potentially predicting a better response to anti IL-5r in patients fully eligible for both mepolizumab and benralizumab and suggests that in late non responder patients to mepolizumab, more robustly targeting the IL-5 axis may be effective.

Keywords: benralizumab; clinical response; mepolizumab; severe eosinophilic asthma; switch.

Figure 1

Distribution of clinical characteristics of patients ((A): lung function expressed as FEV1%; (B): ACT—Asthma Control Test; (C): Oral Corticosteroid daily intake, expressed as mg of prednisone; (D): asthma exacerbation rate; (E): blood eosinophils count; (F): Fractional Exhaled Nitric Oxide) at baseline and follow-up examinations by subgroup: non-switch (black boxes) and switch (grey boxes). 0 m, baseline examination; 6 m, examination at 6 months; switch, examination at the time of switching; f-up, final follow-up examination; triangles represent outliers; * p < 0.05, ** p < 0.01, *** p < 0.001 for comparisons with the examination at 6 months; dashed lines indicate p > 0.05. #, one point omitted for graphical reasons (eosinophils = 15,000 per µL for one patient of the non-switch subgroup, baseline examination).