Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study)

Abstract

Background Benralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness. Methods This is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization. Results Twenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99–3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55–3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65–2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51–1.85; p = 0.007)]. Conclusions These results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.

Effectiveness of Switching to Benralizumab in Severe Refractory Eosinophilic Asthma

“…In our series, functional parameters improved after treatment with benralizumab in both groups (to a greater extent in those previously treated with omalizumab, +302mL, but also in those treated with mepolizumab, +144mL), although the differences were not statistically significant, probably due to the small sample size. Other real-life studies on the efficacy of benralizumab after switching from anti-IL5 biological treatment 28 , 29 or omalizumab obtain efficacy data similar to those found in our series. 26 …”

Comparison between clinical trials and real-world evidence studies on biologics for severe asthma

“…In this regard, we have seen that some RWE studies are beginning to provide interesting evidence. [99][100][101][102][103][104][105][106][107][108] In the context of national and international registries and large databases, RWE studies can go beyond one of their most significant limitations, which is the low number of patients examined. 117,118 Big data obtained from networks and registers will also allow us to define alternative treatment schemes and dosages, but it is currently necessary to refer to those available.…”

“…Other very recent observational studies, retrospective studies, and multicentre studies confirmed that patients with SEA and heterogeneous baseline characteristics treated with benralizumab showed clinically significant improvement in asthma control, QoL, and OCS-sparing effect. 106 , 107 To identify new biomarkers with potentially predictive characteristics, a group of Italian researchers conducted real-life studies on anti-IL-5/anti-IL-5R mAbs using a proteomic approach. They found interesting and innovative data, such as increased oxidation levels of ceruloplasmin and transthyretin in patients treated with benralizumab and apolipoprotein A1 oxidation after mepolizumab treatment ( Table 4 ).…”

Response to monoclonal antibodies in asthma: definitions, potential reasons for failure and therapeutic options for suboptimal response

“…Other studies have also explored the effect of switching to another mAb on residual disease after blocking the IL-5 pathway. The ORBE study, an observational, retrospective, multicentre study in real-life conditions in Spain, characterized the patient profile and evaluated the effectiveness of at least the first three benralizumab doses in 19 severe eosinophilic asthma patients, refractory to anti-IL5 mAbs [78]: 88.9% of the included patients had been previously treated with mepolizumab, and 11.1% with reslizumab, although in some cases, there was a washout period between previous treatment and benralizumab treatment initiation at the investigator's discretion. The J Investig Allergol Clin Immunol 2023; Vol.…”