Case Report Describes Resolution of AD During Phase 3 Trial of Asthma Biologic

A recent case report details how a teenage participant in a phase 3 pivotal trial for a biologic for severe asthma had her atopic dermatitis (AD) clear up as well.

The drug, benralizumab, is only indicated for the treatment of eosinophilic asthma.

In January 2015, a 14-year-old female with severe, uncontrolled asthma was enrolled in CALIMA, a randomized, double-blind, parallel-group, placebo-controlled trial for individuals aged 12–75 years who had a history of 2 or more exacerbations in the previous year. In order to be included in the trial, asthma was uncontrolled by medium-dosage to high-dosage inhaled corticosteroids plus long-acting β₂-agonists (ICS plus LABA).

Patients were randomly assigned (1:1:1) to receive 56 weeks of benralizumab 30 mg every 4 weeks, benralizumab 30 mg every 8 weeks, or placebo (all subcutaneous injection).

At enrollment, this patient’s overall baseline asthma symptom score was 3.9 and she had 4 asthma exacerbations in the prior year. In addition, her face was affected by a pruritic, chronic, inflammatory rash consistent with AD. Besides AD, her medical history included allergic rhinitis, multiple food allergies, and allergies to animal dander.

When she entered the trial, her medications included budesonide 160 μg and formoterol 4.5 μg taken as 2 puffs twice a day; montelukast 5 mg once a day; and salbutamol as needed.

Her baseline eosinophil blood count was 1200 cells/μL, her pre-bronchodilator forced expiratory volume in 1 second (FEV1) was 1.9 L and FEV1/forced vital capacity (FVC) ratio was 71.4%, and her post-bronchodilator FEV1 was 3.2 L (FEV1/FVC of 115.9%).

During the study, her asthma symptoms declined (FEV1 at 56 weeks, 3.01 L/110.5% (pre) and 3.25 L/119.3% (post). Her overall asthma symptom score fell to 2.1 and she had just 1 exacerbation, which was triggered by a case of the flu.

The rash on her face resolved spontaneously within the first 5 months of the study. After the unblinding, she was confirmed to have been randomized to benralizumab. Her blood eosinophil count was undetectable after the first dose in the study.

Benralizumab is a biologic that binds directly to the interlukin-5 (IL-5) receptor and eliminates eosinophils and basophils.

“Evidence is increasing that the pathology of asthma, AD, and other diseases that are part of the so-called atopic march are a result of a self-reinforcing and progressive cascade of epithelial barrier dysfunction in the skin, gut mucosa, and respiratory mucosa, allowing increased penetration of allergens and microbes that elicit a systemic, T cell-mediated eosinophilic hyper-response,” noted the author.

The case illustrates how these 2 different conditions may share a related mechanism of action, and how therapies targeting the underlying T cell–eosinophil interaction could potentially be effective in multiple indications, although these would require additional clinical studies.

Reference

Pham DN. Spontaneous resolution of atopic dermatitis incidental to participation in benralizumab clinical trial for severe, uncontrolled asthma: A case report. J Med Case Reports.Published online March 6, 2021. doi: 10.1186/s13256-021-02663-2