ATS 2020: Benralizumab effective in severe eosinophilic asthma in real-world settings
XALOC: Real-world benralizumab use in severe eosinophilic asthma
The XALOC study is the first multicentre real-world study that described the clinical and patient-reported outcomes associated with benralizumab in patients with severe eosinophilic asthma. [Jackson D, et al, ATS 2020 Virtual, abstract P388]
A total of 208 patients (mean age, 50.5 years) who received benralizumab from five specialist asthma centres in the UK were enrolled in the study, with 202 patients having ≥6 months and 180 patients having ≥12 months of follow-up. The patients were assessed at 16, 24 and 48 weeks after initiation of benralizumab.
At baseline, the patients’ median peak eosinophil count was 500 cells/µL. Notably, 43 percent of patients had prior biologic therapy, with the majority having received the anti–IL-5 agent mepolizumab. The majority of patients (84 percent) discontinued prior biologics due to lack of efficacy.
In addition, 61 percent of patients were on maintenance treatment with oral corticosteroids (OCS) at baseline, and 41 percent were on an OCS dosage of >5 mg/day. Eighty-nine percent of patients had ≥1 exacerbation and 75 percent had ≥3 exacerbations in the last 12 months prior to benralizumab initiation. Annualized exacerbation rates in the baseline year were 4.7, 5.3 and 4.0 in the overall, biologic-naïve, and biologic-experienced cohorts, respectively.
Reduction in exacerbations
Overall, the benefits of benralizumab were observed from week 16 and sustained through week 48.
At 48 weeks, 91 percent of patients remained on benralizumab treatment. Compared with baseline, benralizumab reduced exacerbations by 85 percent, 89 percent and 83 percent in the overall cohort, biologic-naïve patients, and biologic-experienced patients, respectively. (Figure)
About half of the patients were free from exacerbations at week 48 regardless of baseline exacerbation risk and prior biologic use. In those with ≥1 exacerbation at baseline, 49 percent were exacerbation-free (56 percent and 43 percent of biologic-naïve and biologic-experienced patients, respectively). Similarly, 52 percent of patients with ≥3 exacerbations at baseline were exacerbation-free at week 48 (57 percent and 47 percent of biologic-naïve and biologic-experienced patients, respectively).
Decrease in OCS use
The exacerbation reduction achieved with benralizumab was accompanied by a decrease in OCS use. Among patients who were on OCS at baseline, 48 percent were off OCS at 48 weeks. Similar effects were observed in biologic-naïve (54 percent) and biologic-experienced patients (41 percent).
Among patients who remained on maintenance OCS, 50 percent were on a daily dosage of ≤5 mg vs 33 percent at baseline. A ≥50 percent reduction in daily OCS dosage was achieved by 61 percent of patients at 48 weeks.
Improvements in patient-reported outcomes
Treatment with benralizumab also resulted in clinically important improvements in patient-reported outcomes. The proportion of patients with well-controlled asthma, as assessed by the Asthma Control Questionnaire-6 (ACQ-6), more than doubled from 8.5 percent at baseline to 20.7 percent after 48 weeks of benralizumab treatment.
More than half of the patients reported clinically important improvements in asthma control (as assessed by ACQ-6) and/or quality of life (QoL) (as assessed by the Standardized Asthma Quality of Life Questionnaire for 12 years and older [AQLQ(S)12+]). (Table)
The real-world results of the XALOC study showed that benralizumab treatment of severe eosinophilic asthma led to improvements in exacerbation rates, OCS use, and patient-reported outcomes. The improvements in clinical outcomes were seen in both biologic-naïve patients and those failing prior biologic therapies.
These results are consistent with those from randomized controlled trials of benralizumab in severe eosinophilic asthma, and confirm the clinical efficacy of benralizumab in a high-risk, difficult-to-treat patient population with a history of poor health outcomes.
ANDHI: Benralizumab improves multiple outcomes
While the efficacy and safety of benralizumab have been well studied, additional data are needed regarding the onset and duration of its clinical effect, improvement in health-related QoL (HRQoL), and potential to treat symptoms of comorbid nasal polyposis. [Lancet 2016;388:2115-2127; Lancet 2016;388:2128-2141; N Engl J Med 2017;376:2448-2458]
ANDHI is a phase IIIb study that evaluated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (defined as blood eosinophil count ≥150 cells/µL) uncontrolled with standard therapy. In this study, 656 patients were randomized to receive benralizumab 30 mg (every 4 weeks for the first three doses, every 8 weeks thereafter) or placebo until week 24. [Harrison TW, et al, ATS 2020 Virtual, abstract 721]
Onset of benefits, HRQoL, nasal polyposis subgroup, safety
At the end of the study, patients receiving benralizumab had a significant 49 percent reduction in annualized exacerbation rate vs placebo recipients (1.86 vs 0.94; p≤0.0001).
Similarly, benralizumab treatment was associated with improvements in forced expiratory volume in 1 second (FEV1) (difference, 160 mL; 95 percent confidence interval [CI], 90 to 230; nominal p<0.0001) and ACQ-6 scores (difference, -0.46; nominal p≤0.001) vs placebo at week 24. These improvements were observed from week 2 onwards.
Clinically meaningful improvements in HRQoL, as assessed by the St George’s Respiratory Questionnaire (SGRQ), with benralizumab vs placebo were evident from week 4 onwards and were maintained at week 24 (difference in scores, -8.11; 95 percent CI, -11.41 to -4.82; p≤0.0001).
Importantly, significant symptomatic improvements were observed from week 4 and maintained over time in patients with comorbid nasal polyposis (difference in Sino-Nasal Outcome Test-22 score, -7.47; 95 percent CI, -13.16 to -1.77; p=0.0105).
The safety profile of benralizumab was comparable with previous reports. Fewer serious adverse events were reported with benralizumab vs placebo (5.4 percent vs 10.9 percent) in the ANDHI study.
The ANDHI study further confirmed the benefits of benralizumab in terms of exacerbation reduction, lung function and HRQoL improvements, and asthma control in patients with severe eosinophilic asthma, and provided evidence on symptom improvement in the subgroup of patients with nasal polyposis.