Dupilumab Reduces Doses of Oral Corticosteroids for Asthma Patients

Mario Castro, MD

New research presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2020 Annual Meeting shows dupilumab could be beneficial in treating a wide range of conditions related to asthma.

A team, led by Mario Castro, MD, University of Kansas School of Medicine, examined whether dupilumab significantly reduced oral corticosteroid maintenance doses, while also improving pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁), independently of baseline eosinophil levels for patients with oral corticosteroid-dependent, severe asthma.

The investigators segmented both patients with allergic rhinitis and without it into either a placebo or treatment arm of the LIBERTY ASTHMA VENTURE trial.

Allergic rhinitis is a common type comorbidity that is reported in approximately 50-70% of asthma patients. This condition contributed to the increased overall disease burden of asthma and is linked to poor asthma control and increased healthcare costs.

Dupilumab is a fully human VelocImmune-derived monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, both known as central drivers of type 2 inflammation in multiple diseases.

Allergic rhinitis was the most frequent atopic coexisting disease in the study population.

In a post hoc analysis, the investigators assessed dupilumab efficacy in patients both with and without self-reported coexisting allergic rhinitis.

The investigators sought endpoints in both patient groups of percentage reduction in oral corticosteroid dose from baseline to week 24, annualized rate of severe asthma exacerbations over 24 weeks, change in pre-BD FEV_1­ from baseline to week 24, and the change in Asthma Control Questionnaire (ACQ-5) values from baseline to week 24.

Overall, dupilumab reduced the oral corticosteroid dose from baseline to week 24 in both patients with and without allergic rhinitis (least squares [LS] mean difference: 32.78% [P <0.0001] and 24.44% [ P= 0.02], respectively). The treatment also reduced the annualized rate of severe asthma exacerbations over 24 weeks when compared to the placebo [(65.5% [P = 0.0004] and 51.1% [P = 0.04]).

Finally, when compared to placebo, dupilumab improved both pre-BD FEV₁ LS mean difference: 0.23L [P = 0.01] and 0.24L [P = 0.008], respectively) and ACQ-5 scores from baseline to week 24.

Overall, there were 6 serious adverse events in the 107-patient placebo arm and 9 serious adverse events in the 103-patient treatment group. The adverse events caused 4 patients in the placebo group and 1 patient in the dupilumab group to discontinue treatment.

Some of the most common adverse events were viral upper respiratory tract infections, bronchitis, sinusitis, influenza, eosinophilia, injection-site reactions, and at least 1 measurement of blood eosinophils greater than 3000 cells/ µL.

In 2018, the US Food and Drug Administration (FDA) approved dupilumab as an add-on maintenance therapy for adults and adolescents aged 12 years or older, with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

In data presented at the CHEST 2019 Annual Meeting in New Orleans, the interleukin 4 and 13 (IL-4; IL-13) targeting monoclonal antibody showed an associated reduction of severe exacerbations and improved lung function in patients with patients both 40 years and younger (early-onset asthma), and older than 40 years (late-onset asthma).

The subgroup assessment of the LIBERTY ASTHMA QUEST study, which observed dupilumab 200 mg or 300 mg as an add-on therapy taken every 2 weeks versus placebo, determined both younger and older patients with asthma can benefit from the biologic.

The original LIBERTY ASTHMA QUEST findings indicated patients with elevated type 2 biomarkers at baseline—as per blood eosinophils ≥150 cells/mcL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb. Investigators conducted this analysis to assess the influence of age at asthma onset on the disease’s course, associated comorbidities, and treatment response.

Patients with later-onset asthma reported a lower mean pre-bronchodilatory FEV₁ (1.52 L) than patients with early-onset asthma (1.88 L), as well as a lesser rate of ongoing atopic condition (71.1% vs 86.6%). The patient groups reported similar baseline mean severe annual exacerbations per patient (2.12 vs 2.08), median levels of blood eosinophils (270 cells/mcL vs 250 cells/mcL), and FeNO (26 ppb vs 24 ppb).

With 200 mg dupilumab versus placebo, patients reported a 38.1% reduction in severe exacerbations (P = .0009) in early-onset asthma, and a 63.7% reduction in severe exacerbations (P <.0001) in late-onset asthma.

With 300 mg dupilumab versus placebo, patients reported a 37.3% reduction in severe exacerbations (P = .0007) in early-onset asthma, and a 68.5% reduction in severe exacerbations (P <.0001) in late-onset asthma.