Mepolizumab improves small airway function in severe eosinophilic asthma

Farah, Claude S.; Badal, Tanya; Reed, Nicola; Rogers, Peter G.; King, Gregory G.; Thamrin, Cindy; Peters, Matthew J.; Seccombe, Leigh M.

doi:10.1016/j.rmed.2019.01.016

Cited by 50 publications

(34 citation statements)

References 27 publications

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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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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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“…Farah et al [13] assessed ventilation inhomogeneity in 20 adults with severe eosinophilic asthma, using multiple‐breath nitrogen washout to measure global (lung clearance index (LCI)) and regional ventilation inhomogeneity in acinar (Sacin) and conducting (Scond) airways. They report significant improvements in small airway function following mepolizumab.…”

Section: Discussionmentioning

confidence: 99%

Imaging for precision medicine: can V‐P SPECT measure mepolizumab response in asthma?

McDonald

Urroz

Bajc

et al. 2021

Respirology Case Reports

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Monoclonal antibody therapies are effective for many but not all people with severe asthma. Precision medicine guides treatment selection using biomarkers to select patients most likely to respond according to their inflammatory endotypes. However, when assessing response to treatment, greater precision is required. We report a case series describing treatment response to mepolizumab in four severe asthma patients, assessed by traditional methods and with objective ventilation/perfusion single photon emission computed tomography (V-P SPECT). In this series, patients with severe asthma received mepolizumab treatment with clinical outcomes recorded at commencement and at approximately 16 weeks post-treatment initiation. V-P SPECT imaging was performed before and after treatment to determine ventilation heterogeneity and perfusion, and its ability to assess treatment responsiveness. V-P SPECT shows promise as an objective measure to assess lung ventilation and perfusion to observe and assess responsiveness to mepolizumab. With quantification, this measure may allow better precision in determining treatment improvements.

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“…The investigators reported that only beclomethasone dipropionate/formoterol achieved a significant improvement in the cumulative methacholine provocation dose and a trend toward a reduction in closing capacity. 174 Farah and colleagues 175 noted that the anti-IL-5 monoclonal antibody mepolizumab was able to improve lung ventilation heterogeneity indexes in subjects with severe asthma after 26 weeks of treatment. Compared with placebo, omalizumab, a monoclonal antibody targeting serum immunoglobulin E, failed to demonstrate a significant reduction in alveolar NO in subjects with moderate to severe asthma.…”

Section: Delivery Systems Targeting Small Airwaysmentioning

confidence: 99%