Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life

Sposato, Bruno; Camiciottoli, Gianna; Bacci, Elena; Scalese, Marco; Carpagnano, Giovanna Elisiana; Pelaia, Corrado; Santus, Pierachille; Maniscalco, Mauro; Masieri, Simonetta; Corsico, Angelo Guido; Scichilone, Nicola; Baglioni, Stefano; Murgia, Nicola; Folletti, Ilenia; Bardi, Giulio; Grosso, Amelia; Cameli, Paolo; Latorre, Manuela; Musarra, Antonino; Bargagli, Elena; Rícci, Alberto; Pelaia, Girolamo; Paggiaro, Pierluigi; Rogliani, Paola

doi:10.1016/j.pupt.2020.101899

Cited by 52 publications

(48 citation statements)

References 32 publications

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“…FeNO 50 is widely accepted in asthma as a useful biomarker for prediction of exacerbation and compliance with inhalation therapy [29], while CaNO has been proposed in the literature as a reliable biomarker of small airway inflammation [29, 30]. In line with our results, previous studies have reported a significant decrease in FeNO 50 after at least 6 months of mepolizumab treatment [31, 32], but no differences after the first dose [33]. This result was further confirmed by J’awNO, a flow-independent marker of bronchial NO flux, that showed the same pattern.…”

Section: Discussionsupporting

confidence: 89%

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Cameli

Bergantini

d’Alessandro

et al. 2020

Int Arch Allergy Immunol

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Introduction: Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms. Objective: To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients. Population and Methods: We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires. Results: A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed. Conclusions: Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.

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Section: Discussionsupporting

confidence: 89%

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Cameli

Bergantini

d’Alessandro

et al. 2020

Int Arch Allergy Immunol

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“…Thus, from our experience the results are more favourable than those from the SIRIUS study (6), where 235 of the patients treated with Mepolizumab experienced a reduction of 90-100% of dose in the use of OCS with respect to placebo (11%), and 64% experienced some degree of reduction in the daily dose of OCS. In the Sposato et al study (17), where they retrospectively included 134 asthma patients treated with Mepolizumab, the OCS were withdrawn in 45.6% of the patients, with similar values to those observed in our study. These figures are slightly higher in the study by Caminati et al (18) where OCS were removed in 56% of the patients.…”

Section: Discussionsupporting

confidence: 88%

“…The results show a clear improvement for the patients, which is reflected in a reduction of the number of exacerbations, improved clinical control, and a reduction in the use of OCS. The data are very similar to those in the literature, both in the controlled clinical trials (5-9) and in the real-life studies carried out with the drug (11,(15)(16)(17)(18). In this way, the type of patients included in our series are very similar to those already published, both in existence of associated comorbidities and in the presence of secondary effects attributed to the administration of the drug.…”

Section: Discussionsupporting

confidence: 87%

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Clinical Experience in the Treatment of Severe Eosinophilic Asthma With Mepolizumab

Rodríguez

Valverde

Álvarez

et al. 2020

Preprint

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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.

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“…Furthermore, pre-treatment IOS measures of SAD demonstrated to be meaningful predictors of clinical response, thereby indicating that severe SAD might describe a distinct phenotype with therapeutic implications among patients with severe eosinophilic asthma. Our results are consistent with the findings of previous studies which indicated that measures of SAD like FEF 25-75 , lung clearance index, regional ventilation inhomogeneity in acinar and conducting airways improve significantly under biological therapy [20,21]. Oscillometric measures of SAD seem to be feasible tools in selecting appropriate patients qualifying for anti-T2 biological therapy beyond the rather crude measurement of baseline blood eosinophils count that is frequently influenced by a multitude of factors, e.g.…”

Section: Table 2 Area Under the Curve (Auc) Of Clinical Predictorssupporting

confidence: 91%

Small airway dysfunction as predictor and marker for clinical response to biological therapy in severe eosinophilic asthma: a longitudinal observational study

et al. 2020

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Background Anti-T2 biological therapies have proven to effectively reduce acute exacerbations and daily doses of oral steroids in severe eosinophilic asthma. Despite the remarkable clinical efficacy, there are usually only moderate improvements in airflow limitation, suggesting that other measures of lung function like small airway dysfunction (SAD) might better reflect the clinical response. We aimed to investigate if measures of small airway function would predict and correlate with the clinical response to anti-T2 therapy. Methods We studied data of patients who were previously included in the German prospective longitudinal All Age Asthma Cohort (ALLIANCE) that recruits asthma patients of all severity grades and inflammatory phenotypes. The selection criteria for this analysis were adult patients with severe eosinophilic asthma under treatment with anti-T2 biological agents. Asthma control was assessed by asthma control test (ACT) and number of severe exacerbations. Small airway function was assessed by the frequency dependence of resistance (FDR, R5-20)) derived from impulse oscillometry (IOS) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75). We also studied air trapping (RV and RV/TLC), blood eosinophils and FeNO. Patients were classified into responders and partial or non-responders. Clinical response was defined as at least 50% reduction in annualized severe exacerbations and daily oral steroid doses accompanied with a minimum increase of 3 points in the ACT score. We used a Receiver Operator Characteristic (ROC) to study the capacity of FDR in predicting clinical response compared to other clinical variable like blood eosinophils. We studied the correlation between FDR measures and clinical response, represented by the ACT score and number of exacerbations, using linear regressions. Results 20 patients were included (mean age, 59 ± 9 years; 60% female; mean body mass index (BMI), 27.6 ± 5.4 kg/m2; mean absolute blood eosinophils, 570 ± 389/µl; mean number of severe exacerbations 12 months prior to initiating the biological therapy, 5.0 ± 3; mean predicted FEV1, 76 ± 21%; mean predicted FDR, 224 ± 140%; mean daily prednisolone dose, 6.4 ± 4.9 mg; mean ACT score, 15 ± 5). Responders had significantly higher baseline FDR compared to partial or non-responders but similar FEV1, FEF25–75, RV and RV/TLC. ROC analysis showed that the combination of FDR and blood eosinophils had the best predictive capacity of the clinical response among all tested clinical markers (FeNO, FEV1, FDR, blood eosinophils) with an AUC of 85% [67–100%], (CI = 0.95, p = 0.01). Linear regressions indicated better associations between improvements in FDR and ACT score (R2 = 0.42, p = 0.001) than with FEV1 and ACT score (R2 = 0.25, p = 0.013). Likewise, we observed better associations between improvements in FDR and reduction of exacerbations (R2 = 0.41, p = 0.001) than with FEV1 (R2 = 0.20, p = 0.025). Conclusion Our data suggest that severe SAD may represent a distinct phenotype of eosinophilic asthma that substantially improves under anti-T2 biological therapy. Measures of small airway function might be useful in selecting appropriate patients qualifying for anti-T2 biological therapy in addition to blood eosinophil count.

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Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life

Cited by 52 publications

References 32 publications

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Clinical Experience in the Treatment of Severe Eosinophilic Asthma With Mepolizumab

Small airway dysfunction as predictor and marker for clinical response to biological therapy in severe eosinophilic asthma: a longitudinal observational study

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