Suboptimal treatment response to anti-IL-5 monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena

2020 ◽  
Vol 56 (4) ◽  
pp. 2000117 ◽  
Author(s):  
Manali Mukherjee ◽  
David Felipe Forero ◽  
Stephanie Tran ◽  
Marie-Eve Boulay ◽  
Mylène Bertrand ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Immune Complex ◽  
Complement Activation ◽  
Late Onset ◽  
Real Life ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Number Of Patients ◽  
Autoimmune Phenomena

BackgroundIn clinical trials, the two anti-interleukin (IL)-5 monoclonal antibodies (mAbs: mepolizumab and reslizumab) approved to treat severe eosinophilic asthma reduce exacerbations by ∼50–60%.ObjectiveTo observe response to anti-IL-5 mAbs in a real-life clinical setting, and to evaluate predictors of suboptimal response.MethodsIn four Canadian academic centres, predefined clinical end-points in 250 carefully characterised moderate-to-severe asthmatic patients were collected prospectively to assess response to the two anti-IL-5 mAbs. Suboptimal response was determined based on failure to reduce maintenance corticosteroid (MCS) or asthma symptoms scores (Asthma Control Questionnaire (ACQ)) or exacerbations, in addition to persistence of sputum/blood eosinophils. Worsening in suboptimal responders was assessed based on reduced lung function by 25% or increase in MCS/ACQ. A representative subset of 39 patients was evaluated for inflammatory mediators, autoantibodies and complement activation in sputum (by ELISA) and for immune-complex deposition by immunostaining formalin-fixed paraffin-embedded sputum plugs.ResultsSuboptimal responses were observed in 42.8% (107 out of 250) patients treated with either mepolizumab or reslizumab. Daily prednisone requirement, sinus disease and late-onset asthma diagnoses were the strongest predictors of suboptimal response. Asthma worsened in 13.6% (34 out of 250) of these patients. The majority (79%) of them were prednisone-dependent. Presence of sputum anti-eosinophil peroxidase immunoglobulin (Ig)G was a predictor of suboptimal response to an anti-IL-5 mAb. An increase in sputum C3c (marker of complement activation) and deposition of C1q-bound/IL-5-bound IgG were observed in the sputa of those patients who worsened on therapy, suggesting an underlying autoimmune-mediated pathology.ConclusionA significant number of patients who meet currently approved indications for anti-IL5 mAbs show suboptimal response to them in real-life clinical practice, particularly if they are on high doses of prednisone. Monitoring blood eosinophil count is not helpful to identify these patients. The concern of worsening of symptoms associated with immune-complex mediated complement activation in a small proportion of these patients highlights the relevance of recognising airway autoimmune phenomena and this requires further evaluation.

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data

2021 ◽  
pp. 1-13
Author(s):  
Betül Özdel Öztürk ◽  
Zeynep Yavuz ◽  
Dilek Eraslan ◽  
Dilşad Mungan ◽  
Yavuz Selim Demirel ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Real Life ◽  
Blood Eosinophil ◽  
Life Questionnaire ◽  
Eosinophilic Asthma ◽  
Quality Of Life Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
Median Dosage ◽  
Act Score

<b><i>Background:</i></b> Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. <b><i>Methods:</i></b> The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. <b><i>Results:</i></b> A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/μL to 89/μL and 85/μL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. <b><i>Conclusion:</i></b> Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

scholarly journals Mepolizumab effectiveness and identification of super-responders in severe asthma

2020 ◽  
Vol 55 (5) ◽  
pp. 1902420 ◽  
Author(s):  
Erin S. Harvey ◽  
David Langton ◽  
Constance Katelaris ◽  
Sean Stevens ◽  
Claude S. Farah ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Real World ◽  
Rate Ratio ◽  
Disease Burden ◽  
Symptom Control ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Peripheral Blood Eosinophil ◽  
Severe Eosinophilic Asthma

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

Clinical Experience in the Treatment of Severe Eosinophilic Asthma With Mepolizumab

2020 ◽  
Author(s):  
Ana Isabel Enríquez Rodríguez ◽  
Tamara Hermida Valverde ◽  
Pedro Romero Álvarez ◽  
Francisco Julián López González ◽  
Jose Antonio Gullón Blanco ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Blood Count ◽  
Real Life ◽  
Questionnaire Data ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Multicentric Study ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Life Conditions

Abstract Introduction: Severe eosinophilic asthma is an incapacitating disease requiring the patient to take many drugs, amongst which are oral corticoids (OCS), for its control. Mepolizumab is a monoclonal antibody capable of blocking the binding of Interleukin 5 (IL-5) to the eosinophils, and, in this way reducing the exacerbations, symptoms and need for OCS. Our objective was to evaluate the experience with this drug on patients being treated for severe asthma in real-life conditions. Methods: Retrospective, multicentric study carried out in eight hospitals in the Principality of Asturias, in which the demographic, clinical, analytical, lung function and ACT (Asthma Control Questionnaire) data of the patients with severe eosinophilic asthma being treated with Mepolizumab for three years were collected. Results: Sixty-nine patients (72% women) were included, with a mean age of 56±13 years. The eosinophil blood count before treatment was 856 cels/mm3 (SD 754), decreasing after 6 months to 101 cels/mm3 (SD 98). Annual exacerbations decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p=0.001), while the FEV1% increased from 68% (SD 20) to 76% (SD 21) (<0.001). At the onset 25 patients (36%) were using OCS ( 18 mg/day of prednisone) and after treatment this decreased to 13 (19%) ( 9mg/day of prednisone) ( p=0.000), with complete withdrawal in 12 (48%). The response to Mepolizumab was positive in 56 patients (81%), and no adverse effects were observed. Conclusions: Mepolizumab has demonstrated to be efficacious and safe in real life in the treatment of patients with badly controlled eosinophilic asthma.

scholarly journals Mepolizumab improves sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study

2021 ◽  
Vol 15 ◽  
pp. 175346662110093
Author(s):  
Aikaterini Detoraki ◽  
Eugenio Tremante ◽  
Maria D’Amato ◽  
Cecilia Calabrese ◽  
Claudia Casella ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Asthma Control ◽  
Real Life ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Nasal Symptoms ◽  
Asthma Patients ◽  
Nasal Cytology ◽  
Snot 22

Background: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. Methods: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. Results: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0–T12 p < 0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0–T12 p = 0.99). A significant improvement of %FEV1, ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p < 0.001). Conclusions: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life. The reviews of this paper are available via the supplemental material section.

Mepolizumab Effectiveness and Allergic Status in Real Life

2020 ◽  
pp. 1-8
Author(s):  
Bruno Sposato ◽  
Marco Scalese ◽  
Gianna Camiciottoli ◽  
Giovanna Elisiana Carpagnano ◽  
Corrado Pelaia ◽  
...  
Keyword(s):  
Oral Corticosteroid ◽  
Real Life ◽  
Blood Eosinophil ◽  
Test Results ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Prick Test ◽  
Significant Relationships ◽  
Therapeutic Choice ◽  
Β2 Agonists

<b><i>Background:</i></b> It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. <b><i>Objective:</i></b> We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. <b><i>Method:</i></b> We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; <i>n</i>: 97–72.4%), and nonallergic, with no prick test results and normal IgE levels &#x3c;100 UI/mL (severe nonallergic eosinophilic asthma [SNAEA]; <i>n</i>: 37–27.6%). They had taken mepolizumab for at least 6 months. <b><i>Results:</i></b> After 10.9 ± 3.7 months, improvements in FEV<sub>1</sub>%, FEF<sub>25–75</sub>%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting β2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5–9]) than in SAEA (5 [2.5–8.5]; <i>p</i> = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV<sub>1</sub> &#x3e;80%, FEF<sub>25–75</sub> &#x3e;65%, exacerbations ≤2, BE &#x3c;300 cells/µL, and FENO &#x3c;25 ppb between SAEA and SNAEA. Besides, no significant relationships were found, comparing SNAEA with SAEA, for FEV<sub>1</sub>% (β = −0.110; <i>p</i> = 0.266), FEF<sub>25–75</sub>% (β = −0.228; <i>p</i> = 0.06), BE counts (β = −0.012; <i>p</i> = 0.918), FENO (β = 0.234; <i>p</i> = 0.085), ACT (β = 0.046; <i>p</i> = 0.660), and exacerbations (β = −0.070; <i>p</i> = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV<sub>1</sub> &#x3e;80%: OR = 1.04 [95% CI: 0.43–2.55], <i>p</i> = 0.923; FEF<sub>25–75</sub> &#x3e;65%: OR = 0.41 [95% CI: 0.08–2.03], <i>p</i> = 0.272) were detected. Neither all other parameters, such as ACT &#x3e;20 (OR = 0.73 [95% CI: 0.32–1.63], <i>p</i> = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55–3.27], <i>p</i> = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40–3.39], <i>p</i> = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40–29.27], <i>p</i> = 0.258), were differently associated with 1 or the other phenotype. <b><i>Conclusion:</i></b> Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.

scholarly journals Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1822
Author(s):  
Corrado Pelaia ◽  
Claudia Crimi ◽  
Santi Nolasco ◽  
Giovanna Elisiana Carpagnano ◽  
Raffaele Brancaccio ◽  
...  
Keyword(s):  
Life Experience ◽  
Symptom Control ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Biologic Treatment ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Severe Eosinophilic Asthma

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

scholarly journals Effectiveness of mepolizumab in a real-life cohort of patients with severe refractory eosinophilic asthma and multiple comorbidities

2020 ◽  
Author(s):  
Claudia Crimi ◽  
Raffaele Campisi ◽  
Giulia Cacopardo ◽  
Rossella Intravaia ◽  
Santi Nolasco ◽  
...  
Keyword(s):  
Treatment Response ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Life Effectiveness ◽  
Blood Eosinophil Count ◽  
Severe Eosinophilic Asthma ◽  
Act Score

AbstractBACKGROUNDPatients with severe asthma often suffer from comorbidities whose impact on the course of biological therapy has not been elucidated yet.OBJECTIVETo evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities who received mepolizumab (MEPO) for the treatment of severe eosinophilic asthma (EA).METHODSHealth records of 31 patients were retrospectively analyzed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 second (FEV1), FEV1% of predicted and FEV1/FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), nine (T6) and 12 months (T12). A clinical response was defined as: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV1 increase ≥ 200 mL.RESULTSAt T12 blood eosinophil level decreased by 89.89% (p>0.0001), an improvement in ACT of 3 points from baseline was recorded in 80.65% of patients (p>0.0001) and 96.77% of patients reduced by minimum 30% the number of exacerbations (p>0.0001). 84% of patients discontinued OCS (p>0.0001). FEV1 increased by 0.22 (p=0.0224) while FEV1/FVC was statistically significant only at T1. No significant differences were generally found among patients with a specific comorbidity. The number of comorbidities did not influence treatment response. Neither the comorbidities nor other characteristics (sex, BMI, age, smoking, baseline eosinophil level) influenced treatment response.CONCLUSIONSMEPO in patients with severe EA is effective regardless of the presence of one or more comorbidities.

scholarly journals Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mark C. Liu ◽  
Bradley Chipps ◽  
Xavier Munoz ◽  
Gilles Devouassoux ◽  
Miguel Bergna ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
High Dose ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Post Hoc Analysis ◽  
Severe Eosinophilic Asthma ◽  
Baseline Characteristics ◽  
Post Hoc

Abstract Background The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response. Methods This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders—i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George’s Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction). Results Of the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index. Conclusions After switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics. Trial registration This manuscript is a post hoc analysis of data from the OSMO study. ClinicalTrials.gov, NCT02654145. Registered January 13, 2016.

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