Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm: A Post Hoc Analysis from the ANANKE Study

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300-450 cells/mm subset of patients.

Patients And Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300-450 cells/mm subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.

Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300-450 cells/mm. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300-450 subset showed similar reductions in AER (-94.8% vs -92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.

Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300-450 cells/mm subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300-450 patients as in the total population.

Citing Articles

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

Yamaguchi M, Nishimura Y, Takumi Y, Hayashi N, Sakamoto K, Tohda Y J Asthma Allergy. 2024; 17:45-60.

PMID: 38268535 PMC: 10807277. DOI: 10.2147/JAA.S432695.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

Vultaggio A, Aliani M, Altieri E, Bracciale P, Brussino L, Caiaffa M Respir Res. 2023; 24(1):135.

PMID: 37210543 PMC: 10200058. DOI: 10.1186/s12931-023-02439-w.

References

Korn S, Bourdin A, Chupp G, Cosio B, Arbetter D, Shah M . Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years. J Allergy Clin Immunol Pract. 2021; 9(12):4381-4392.e4. DOI: 10.1016/j.jaip.2021.07.058. View

Bumbacea D, Campbell D, Nguyen L, Carr D, Barnes P, Robinson D . Parameters associated with persistent airflow obstruction in chronic severe asthma. Eur Respir J. 2004; 24(1):122-8. DOI: 10.1183/09031936.04.00077803. View

Menzella F, Fontana M, Galeone C, Ghidoni G, Capobelli S, Ruggiero P . Real world effectiveness of benralizumab on respiratory function and asthma control. Multidiscip Respir Med. 2021; 16(1):785. PMC: 8506201. DOI: 10.4081/mrm.2021.785. View

Price D, Trudo F, Voorham J, Xu X, Kerkhof M, Jie J . Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11:193-204. PMC: 6121746. DOI: 10.2147/JAA.S176026. View

Dagher R, Kumar V, Copenhaver A, Gallagher S, Ghaedi M, Boyd J . Novel mechanisms of action contributing to benralizumab's potent anti-eosinophilic activity. Eur Respir J. 2021; 59(3). PMC: 8923056. DOI: 10.1183/13993003.04306-2020. View

Brusselle G, Koppelman G . Biologic Therapies for Severe Asthma. N Engl J Med. 2022; 386(2):157-171. DOI: 10.1056/NEJMra2032506. View

Pelaia C, Busceti M, Vatrella A, Rago G, Crimi C, Terracciano R . Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm Pharmacol Ther. 2019; 58:101830. DOI: 10.1016/j.pupt.2019.101830. View

Tan W, Bourbeau J, Nadeau G, Wang W, Barnes N, Landis S . High eosinophil counts predict decline in FEV: results from the CanCOLD study. Eur Respir J. 2020; 57(5). DOI: 10.1183/13993003.00838-2020. View

Bleecker E, FitzGerald J, Chanez P, Papi A, Weinstein S, Barker P . Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388(10056):2115-2127. DOI: 10.1016/S0140-6736(16)31324-1. View

10.

Price D, Rigazio A, Campbell J, Bleecker E, Corrigan C, Thomas M . Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015; 3(11):849-58. DOI: 10.1016/S2213-2600(15)00367-7. View

11.

Jackson D, Burhan H, Menzies-Gow A, Pfeffer P, Nanzer A, Garcia Gil E . Benralizumab Effectiveness in Severe Asthma Is Independent of Previous Biologic Use. J Allergy Clin Immunol Pract. 2022; 10(6):1534-1544.e4. DOI: 10.1016/j.jaip.2022.02.014. View

12.

FitzGerald J, Bleecker E, Nair P, Korn S, Ohta K, Lommatzsch M . Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; 388(10056):2128-2141. DOI: 10.1016/S0140-6736(16)31322-8. View

13.

Sullivan P, Ghushchyan V, Globe G, Schatz M . Oral corticosteroid exposure and adverse effects in asthmatic patients. J Allergy Clin Immunol. 2017; 141(1):110-116.e7. DOI: 10.1016/j.jaci.2017.04.009. View

14.

FitzGerald J, Bleecker E, Menzies-Gow A, Zangrilli J, Hirsch I, Metcalfe P . Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2017; 6(1):51-64. DOI: 10.1016/S2213-2600(17)30344-2. View

15.

Kraft M, Brusselle G, FitzGerald J, Pavord I, Keith M, Fageras M . Patient characteristics, biomarkers and exacerbation risk in severe, uncontrolled asthma. Eur Respir J. 2021; 58(6). DOI: 10.1183/13993003.00413-2021. View

16.

Paoletti G, Di Bona D, Chu D, Firinu D, Heffler E, Agache I . Allergen immunotherapy: The growing role of observational and randomized trial "Real-World Evidence". Allergy. 2021; 76(9):2663-2672. DOI: 10.1111/all.14773. View

17.

Bourdin A, Molinari N, Vachier I, Pahus L, Suehs C, Chanez P . Mortality: a neglected outcome in OCS-treated severe asthma. Eur Respir J. 2017; 50(5). DOI: 10.1183/13993003.01486-2017. View

18.

Pelaia C, Busceti M, Crimi C, Carpagnano G, Lombardo N, Terracciano R . Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma. Biomed Pharmacother. 2020; 129:110444. DOI: 10.1016/j.biopha.2020.110444. View

19.

Backman H, Lindberg A, Hedman L, Stridsman C, Jansson S, Sandstrom T . FEV decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort. World Allergy Organ J. 2020; 13(3):100110. PMC: 7082214. DOI: 10.1016/j.waojou.2020.100110. View

20.

Nolasco S, Crimi C, Pelaia C, Benfante A, Caiaffa M, Calabrese C . Benralizumab Effectiveness in Severe Eosinophilic Asthma with and without Chronic Rhinosinusitis with Nasal Polyps: A Real-World Multicenter Study. J Allergy Clin Immunol Pract. 2021; 9(12):4371-4380.e4. DOI: 10.1016/j.jaip.2021.08.004. View