Long-Term Clinical Remission on Benralizumab Treatment in Severe Eosinophilic Asthma: A Four-Year Real-Life Study

Abstract

Background: The current availability of monoclonal antibodies against key mediators of type-2 (T2) inflammation has led to a redefinition of the ultimate objectives of severe asthma treatment to a more composite concept of disease remission. Objectives: The aim of this real-life study was to estimate the percentage of patients who achieved clinical remission over 4 years of treatment with benralizumab, and to identify baseline predictors for the achievement of such a composite outcome in the long term. Methods: Data from a 4-year follow-up of 23 patients who were prescribed benralizumab as an add-on therapy because of uncontrolled severe eosinophilic asthma were retrospectively analyzed and compared. Clinical remission was considered to be "complete" if oral corticosteroid (OCS) use was not required, there were no exacerbations, an asthma control test (ACT) score ≥ 20 was achieved and a pre-bronchodilation percent predicted a forced expiratory volume in 1 s (FEV₁%) ≥ 80%. Clinical remission was considered to be "partial" if OCS use was not required, plus at least two of the other three aforementioned criteria. Results: The overall percentage of patients who achieved clinical remission was 86.9% after 12 months, and 91.3% after 24 and 48 months of treatment. The rate of complete remission over partial remission increased over time. After 12 months of treatment, 65% of patients fulfilled the criteria for complete remission and 35.0% for partial remission. After 48 months of treatment, 71.4% of patients were in a status of complete remission and 28.6% in a status of partial remission. A long-term composite outcome of complete clinical remission was more likely to be achieved by severe eosinophilic asthma patients with comorbid nasal polyposis, bronchiectasis and osteoporosis, and with OCS dependency, a predicted pre-bronchodilation FEV₁% ≥ 80% and a predicted FEF_25-75% < 65% at baseline. Conclusions: Our real-life experience suggests that treatment with benralizumab may allow the achievement and long-term maintenance of clinical remission in a high percentage of severe eosinophilic asthma patients, up to 4 years of follow-up.

Keywords: asthma; benralizumab; non-invasive biomarkers.

Figure 1

Benralizumab effectiveness on: (A) number of exacerbations/year (mean with range); (B) percentage of patients experiencing exacerbations. Statistically significant differences vs. baseline are highlighted with *. Abbreviations: T₀ = baseline; T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months.

Figure 2

Benralizumab effectiveness on: (A) Dosage of oral prednisone required (mean with SD); (B) Percentage of patients requiring OCS. Statistically significant differences vs. baseline are highlighted with *. Abbreviations: T₀ = baseline; T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months; OCS = oral corticosteroids.

Figure 3

Benralizumab effectiveness on: (A) percentage of predicted pre-bd FEV₁% (mean with SD); (B) pre-bd FEV₁ in liters (mean with SD); (C) predicted pre-bd FEF_25–75% (mean with SD). Statistically significant differences vs. baseline are highlighted with *. Abbreviations: T₀ = baseline; T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months; FEV₁ = forced expiratory volume in 1 s; FEF_25–75% = forced expiratory flow between 25% and 75% of vital capacity.

Figure 4

Benralizumab effectiveness on the ACT score (mean with SD). Statistically significant differences vs. baseline are highlighted with *. Abbreviations: T₀ = baseline; T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months; ACT = asthma control test score.

Figure 5

Benralizumab effectiveness on markers of asthma-related T2 inflammation: (A) blood eosinophil count (mean with SD); (B) FeNO₅₀ levels (mean with SD); (C) total IgE levels (mean with SD). Statistically significant differences vs. baseline are highlighted with *. Abbreviations: T₀ = baseline; T₆ = 6 months; T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months; FeNO₅₀ = fractional exhaled nitric oxide at a flow rate of 50 mL/s; IgE = immunoglobulin E.

Figure 6

Patients on complete and partial remission with benralizumab at T₁₂, T₂₄ and T₄₈. Abbreviations: T₁₂ = 12 months; T₂₄ = 24 months; T₃₆ = 36 months; T₄₈ = 48 months.

Figure 7

Strength of association in terms of odds ratio (OR) between baseline characteristics and clinical remission (complete and partial) vs. no remission after 4 years of treatment with benralizumab. Statistically significant results are highlighted with *. Abbreviations: BMI = body mass index; ASA sensitivity = sensitivity to aspirin; OSAS = obstructive sleep apnea syndrome; FEV₁ = forced expiratory volume in 1 s; FEF_25–75% = forced expiratory flow between 25% and 75% of vital capacity; FeNO₅₀ = fractional exhaled nitric oxide at a flow rate of 50 mL/s.