Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme

Abstract

Background: Pivotal phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection.

Methods: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps).

Results: Out of 1002 patients analysed, 380 were biologic-experienced. At week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130 out of 274) eliminated their use by week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed.

Conclusion: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

In this large, real-world programme, patients with severe eosinophilic asthma treated with benralizumab had substantial improvements in clinical outcomes, irrespective of previous biologic use and key clinical characteristics important to decision-making in clinical practice. ^#: 3 units Asthma Control Test score or −0.5 units in 6-item Asthma Control Questionnaire score. AER: annualised exacerbation rate; MCID: minimal clinically important difference; mOCS: maintenance oral corticosteroid; Q8W: every 8 weeks.

FIGURE 1

Relative reduction in annualised exacerbation rate (AER) from baseline to week 48, overall and according to patients’ previous biologic experience and key baseline clinical characteristics. Analyses are based on patients treated with benralizumab who either discontinued before week 48 or completed 48±4 weeks of follow-up from the index date. The number of patients in each subgroup for the analyses is shown. Baseline data relate to exacerbations during the 12-month baseline period prior to the index date. Week 48 data relate to exacerbations during the follow-up period from the index date to week 48±4. mOCS: maintenance oral corticosteroid; BEC: blood eosinophil count; F_ENO: fractional exhaled nitric oxide; CRSwNP: chronic rhinosinusitis with nasal polyps. ^#: the most recent measurement in the 12-month baseline period; ^¶: based on medical records available at the index date.

FIGURE 2

a) Median maintenance oral corticosteroid (mOCS) daily dose at baseline and week 48, and b) percentage of patients with a 100% reduction in mOCS dose from baseline to week 48, overall and according to patients’ previous biologic experience, among patients who were using mOCS at the index date. Data are based on patients who were using mOCS at the index date and had follow-up data at week 48. The box and whisker plots show the medians, interquartile ranges and minimum and maximum values for mOCS daily dose. ^#: mOCS dose was calculated as the patient's mean daily dosage over the past 30 days on or prior to the target date of the specified visit (the index date or week 48).

FIGURE 3

Mean percentage change in maintenance oral corticosteroid (mOCS) dose from baseline to week 48, overall and according to patients’ previous biologic experience and key baseline clinical characteristics, in patients using mOCS at the index date. mOCS dosage was calculated as a patient's mean daily dosage over the past 30 days on or prior to the target date of the specified visit (the index date or week 48). The number of patients with mOCS use at the index date and with follow-up data at week 48 is shown. BEC: blood eosinophil count; F_ENO: fractional exhaled nitric oxide; CRSwNP: chronic rhinosinusitis with nasal polyposis. ^#: most recent measurement in the 12-month baseline period. ^¶: based on medical records available at the index date.

FIGURE 4

Percentage of patients with improvements matching or exceeding the minimal clinically important difference in Asthma Control Test (ACT) score (3 units) or 6-item Asthma Control Questionnaire (ACQ-6) score (–0.5 units) from baseline to week 48, overall and according to patients’ previous biologic experience and key baseline clinical characteristics. Baseline ACQ-6 and ACT scores were measured at the index date or were the most recent measurement in the 12-month baseline period prior to the index date. The number of patients with ACQ-6 or ACT score data at baseline and week 48±4 is shown. Analyses are based on patients with ACQ-6 or ACT score data at baseline and week 48±4. mOCS: maintenance oral corticosteroid; BEC: blood eosinophil count; F_ENO: fractional exhaled nitric oxide; CRSwNP: chronic rhinosinusitis with nasal polyps. ^#: at the index date or the most recent measurement in the 12-month baseline period; ^¶: based on medical records available at the index date.