Patients with severe eosinophilic asthma controlled on benralizumab may safely minimize high-dose inhaled corticosteroid (ICS) exposure and adverse effects, researchers reported in The Lancet.
Researchers for SHAMAL study (ClinicalTrials.gov Identifier: NCT04159519) sought to assess the potential for benralizumab to safely and effectively reduce use of ICS-formoterol maintenance regimen, to the smallest dose necessary for maintainining asthma control, in patients with severe eosinophilic asthma.
The phase 4, multicenter, randomized, open-label SHAMAL study included adults (aged ≥18 years) diagnosed with severe eosinophilic asthma and controlled asthma on high-dose ICS after initiation of benralizumab. Participants were enrolled from November 12, 2019, to February 16, 2023
The study included a screening visit (visit 1), a 4- to 8-week screening and run-in period, a 32-week reduction period, and a 16-week maintenance period. In the reduction period, patients were randomly assigned 3:1 to the treatment reduction group or the reference group.
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Our findings underscore the opportunity to shift away from high-dose ICS toward a precision-medicine approach with improved outcomes in patients with severe eosinophilic asthma.
The primary endpoint was the proportion of patients who decreased their ICS-formoterol maintenance dose at the end of the reduction period to a medium-dose maintenance and anti-inflammatory reliever treatment (MART), a low-dose MART, or ICS-formoterol as needed.
A total of 168 patients were randomly assigned to the reduction phase, of whom 125 (74%) were assigned to treatment reduction and 43 (26%) to the reference group. The patients had a mean (SD) age of 57.7 (12.2) years, and 53% were female.
At week 32 at the end of the reduction period, 110 (92%) of 119 patients had a decrease in their ICS-formoterol maintenance dose: 18 (15%) to medium-dose ICS-formoterol, 20 (17%) to low-dose ICS-formoterol, and 72 (61%) to ICS-formoterol reliever only.
Among patients in the reduction group, 113 (96%) of 118 participants who had a nonmissing dose maintained the same ICS-formoterol daily dose from week 32 until the end of the maintenance period. The mean change in total daily ICS dose (maintenance plus reliever) from randomization to study end was –1171 μg (standard error [SE], 43.33) for the reduction group and –351 μg (SE, 76.06) for the reference group. The least-squares mean difference in change at week 48 between the 2 groups was –819.82 (95% CI, –992.89 to –646.75).
The mean number of reliever inhalations per week in patients reducing to reliever only by week 32 was 6.3 (7.87), according to another post-hoc analysis. Clinical remission was observed in the reduction group in 48 (56%) participants at week 32 and 48 (54%) at week 48 (5-item Asthma Control Questionnaire score <1.5).
The 2 groups had a comparable annualized asthma exacerbation rate (AER), as the AER was 0.14 (95% CI, 0.09-0.23) in the reduction group and 0.14 (95% CI, 0.06-0.31) in the reference group (rate ratio 1.05 [95% CI, 0.41-2.68]) at the end of the study period.
The rates of adverse events also were similar throughout in the 2 groups, as 91 (73%) participants in the reduction group had adverse events compared with 35 (83%) in the reference group.
Among several limitations, the participants had already responded well to benralizumab and had an eosinophil-driven phenotype, and the effectiveness outcome measures were not part of the study design.
“Our findings underscore the opportunity to shift away from high-dose ICS toward a precision-medicine approach with improved outcomes in patients with severe eosinophilic asthma,” the investigators stated.
Disclosure: This research was funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
