Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study)

Abstract Background Benralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness. Methods This is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization. Results Twenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99–3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55–3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65–2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51–1.85; p = 0.007)]. Conclusions These results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.

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Low Rates of Follow-Up With Primary Care Providers After Pediatric Emergency Department Visits for Respiratory Tract Illnesses

Pediatric Emergency Care ◽

10.1097/pec.0b013e31826c6dde ◽

2012 ◽

Vol 28 (10) ◽

pp. 956-961 ◽

Cited By ~ 16

Author(s):

Danica B. Liberman ◽

Deborah Q. Shelef ◽

Jianping He ◽

Robert McCarter ◽

Stephen J. Teach

Keyword(s):

Primary Care ◽

Emergency Department ◽

Respiratory Tract ◽

Primary Care Providers ◽

Pediatric Emergency ◽

Emergency Department Visits ◽

Pediatric Emergency Department ◽

Care Providers ◽

Respiratory Tract Illnesses

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Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma

European Respiratory Journal ◽

10.1183/13993003.02259-2019 ◽

2020 ◽

Vol 55 (5) ◽

pp. 1902259 ◽

Cited By ~ 5

Author(s):

Gráinne d'Ancona ◽

Joanne Kavanagh ◽

Cris Roxas ◽

Linda Green ◽

Mariana Fernandes ◽

...

Keyword(s):

Clinical Outcomes ◽

Biologic Therapy ◽

Inhaled Corticosteroids ◽

Final Analysis ◽

Good Adherence ◽

Eosinophilic Asthma ◽

Exacerbation Rate ◽

Asthmatic Patients ◽

Severe Eosinophilic Asthma ◽

Asthma Patients

IntroductionInhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.MethodsWe examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74–0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab.ResultsOut of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74–100)% versus 60 (27–100)%; p=0.031) and exacerbations (AER change −2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02–9.94; p=0.045).ConclusionICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.

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Primary Care Follow-up After Emergency Department Visits for Routine Complaints

Pediatric Emergency Care ◽

10.1097/pec.0000000000000314 ◽

2016 ◽

Vol 32 (6) ◽

pp. 371-376 ◽

Cited By ~ 1

Author(s):

Jessica Chen ◽

Eric Singer

Keyword(s):

Primary Care ◽

Emergency Department ◽

Emergency Department Visits

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Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

Journal of Personalized Medicine ◽

10.3390/jpm12010070 ◽

2022 ◽

Vol 12 (1) ◽

pp. 70

Author(s):

Maruša Kopač Šokić ◽

Matija Rijavec ◽

Peter Korošec ◽

Urška Bidovec-Stojkovič ◽

Izidor Kern ◽

...

Keyword(s):

Treatment Strategies ◽

Eosinophilic Inflammation ◽

Asthma Control Test ◽

Sputum Induction ◽

Immunological Parameters ◽

Eosinophilic Asthma ◽

Interleukin 5 ◽

Severe Eosinophilic Asthma ◽

Asthma Patients

Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (p = 0.001), and asthma control test (ACT) (p = 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (p = 0.05), with no difference in IL-5 concentrations (p = 0.743). Peripheral eosinophilia decreased significantly in NR (p = 0.032) and R (p = 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction.

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Benralizumab, an add-on treatment for severe eosinophilic asthma: evaluation of exacerbations, emergency department visits, lung function, and oral corticosteroid use

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s157171 ◽

2018 ◽

Vol Volume 14 ◽

pp. 2059-2068 ◽

Cited By ~ 3

Author(s):

Diego Jose Maselli ◽

Linda Rogers ◽

Jay I Peters

Keyword(s):

Emergency Department ◽

Lung Function ◽

Oral Corticosteroid ◽

Emergency Department Visits ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma

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Effect of Telephone Calls From Primary Care Practices on Follow-up Visits After Pediatric Emergency Department Visits

Archives of Pediatrics and Adolescent Medicine ◽

10.1001/archpediatrics.2009.45 ◽

2009 ◽

Vol 163 (6) ◽

pp. 505 ◽

Cited By ~ 16

Author(s):

Andrew D. Racine ◽

Elizabeth M. Alderman ◽

Jeffrey R. Avner

Keyword(s):

Primary Care ◽

Emergency Department ◽

Pediatric Emergency ◽

Emergency Department Visits ◽

Pediatric Emergency Department ◽

Telephone Calls ◽

Care Practices ◽

Primary Care Practices

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Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme

European Respiratory Journal ◽

10.1183/13993003.02345-2019 ◽

2020 ◽

Vol 55 (6) ◽

pp. 1902345 ◽

Cited By ~ 4

Author(s):

Camille Taillé ◽

Pascal Chanez ◽

Gilles Devouassoux ◽

Alain Didier ◽

Christophe Pison ◽

...

Keyword(s):

Emergency Department Visits ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Early Access ◽

Oral Corticosteroids ◽

Favourable Safety Profile ◽

Access Programme ◽

Clinically Meaningful Outcomes

BackgroundMepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU.MethodsThis retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated.FindingsOverall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL−1 at baseline to 92 cells·µL−1 at 24 months of follow-up; lung function and asthma control followed a similar trend.InterpretationResults confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial.

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