medwireNews: Benralizumab, a monoclonal antibody targeting the interleukin (IL)-5α receptor, significantly reduces treatment failure rates and improves symptoms of eosinophilic exacerbations in people with asthma or chronic obstructive pulmonary disease (COPD), according to results from the phase 2 ABRA trial.
Reporting the findings in The Lancet Respiratory Medicine, Mona Bafadhel (King’s College London, UK) and colleagues describe benralizumab as a “potential biologically driven precision treatment for asthma and COPD exacerbations,” emphasizing that it “achieves better outcomes than the current standard of care with prednisolone alone.”
The multicenter, double-blind, double-dummy trial enrolled 158 adults (54% women, mean age 57 years) between May 2021 and February 2024. Participants included individuals with confirmed diagnoses of COPD (32%), asthma (56%), or both conditions (12%), each with at least one exacerbation in the preceding 12 months and a prior blood eosinophil count exceeding 250 cells/μL.
The patients either presented to emergency departments with acute exacerbations (13%), defined by blood eosinophil counts of at least 300 cells/μL, or at urgent care clinics. The median symptom duration was 5 days.
The participants were then randomly assigned to receive one of three treatment regimens: a single 100 mg subcutaneous injection of benralizumab with oral placebo (BENRA group, n=53) or prednisolone 30 mg (BENRA+PRED group, n=52 patients) daily for 5 days, or a placebo subcutaneous injection plus prednisolone (PRED group, n=53). Nearly all the patients were taking inhaled glucocorticoid therapy before randomization.
The study assessed the rate of treatment failure over 90 days, defined as hospital admission, needing re-treatment, or death, and the total symptom burden at day 28 using a visual analog scale (VAS)
Patients treated with benralizumab, with or without prednisolone, had a significantly lower risk for treatment failure than those receiving prednisolone alone. Over 90 days, treatment failure occurred in 47% of patients in the BENRA group and 42% of those in the BENRA+PRED group versus 74% of patients in the PRED group. For the two BENRA treatment groups pooled, the relative reduction in risk for treatment failure was 74% compared with the PRED group, and the researchers estimate that four patients would need to be treated with benralizumab to prevent one treatment failure.
The superior reduction in treatment failure risk with benralizumab versus prednisone was seen for most subgroups, including patients with asthma or COPD, men and women, and both ex-smokers and never-smokers.
Clarus Leung and Don Sin, both from the University of British Columbia in Vancouver, Canada, also point out in a related comment that “[t]he benefits of benralizumab were evident by 2–3 weeks post-treatment when approximately 50% of patients in the prednisolone alone group had experienced a treatment failure.”
Indeed, the pooled BENRA group had a 61% lower risk for having treatment failure at any given time within 90 days than the PRED group.
In addition, symptom burden at day 28 was significantly lower in the pooled BENRA group than the PRED group, with an average improvement of 49 mm on the VAS. Patients in the pooled BENRA group also showed significant improvements compared with the PRED group on the Medical Research Council Dyspnoea scale (mean difference of 0.39 points), the Asthma Control Questionnaire-7 (mean difference of 0.5 points), and the Asthma Quality of Life Questionnaire (mean difference of 0.53 points).
Adverse events were less frequent in the BENRA and BENRA+PRED groups compared with the PRED group, at respective rates of 77%, 75%, and 91%, with hyperglycemia and sinus infections only occurring in those taking prednisolone. The corresponding rates of serious adverse events were 6%, 2%, and 6%, and there were no deaths.
The authors conclude that “benralizumab is effective as an acute treatment of eosinophilic exacerbations.”
Commentators Leung and Sin congratulate the researchers on their “landmark study,” which they say “highlights the clinical utility of endo-phenotyping of exacerbations with a simple blood biomarker and the effectiveness of anti-IL5 inhibitors in improving health outcomes of patients who experience eosinophil-related exacerbations.”
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Lancet Respir Med 2024; doi:10.1016/S2213-2600(24)00299-6
Lancet Respir Med 2024; doi:10.1016/S2213-2600(24)00323-0
