Mepolizumab effectiveness in patients with severe eosinophilic asthma and co-presence of bronchiectasis: A real-world retrospective pilot study

Crimi, Claudia; Campisi, Raffaele; Nolasco, Santi; Cacopardo, Giulia; Intravaia, Rossella; Porto, Morena; Impellizzeri, Pietro; Pelaia, Corrado; Crimi, Nunzio

doi:10.1016/j.rmed.2021.106491

Cited by 42 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another interesting result that emerges from our data is the confirmation, already seen in previous articles [ 8 , 24 , 25 , 26 , 27 ], that anti-Il-5 and anti-IGE biological therapy have been shown to be effective in reducing blood eosinophilia and in controlling severe asthma, regardless of whether patients also had bronchiectasis not due to CF or ABPA.…”

Section: Discussionsupporting

confidence: 86%

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

Quaranta

Dragonieri

Crimi

et al. 2022

JCM

Self Cite

View full text Add to dashboard Cite

Introduction: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies have been conducted so far to evaluate the role of the leukotriene cysLT/cysLTr1 axis in the management of clinical and inflammatory outcomes within a population of patients with severe asthma and bronchiectasis. The aim of our study was to verify in this population the effect of leukotriene receptor antagonist (LTRA) therapy in clinical and inflammatory control before and after 6 months of introduction of biologic therapy. Methods: We retrospectively enrolled, from eight different severe asthma centers’ outpatients, 36 atopic patients with the simultaneous presence of non-cystic fibrosis (non-CF) and non-allergic bronchopulmonary aspergillosis (non-ABPA) bronchiectasis and severe asthma. The first biological injection was performed at baseline (T0 time). Patients who were already taking LTRA therapy at time T0 were recorded, and no new prescriptions were made. We observed our population over a 6-month period (T1 time). At the baseline we collected the following data: baseline characteristics, clinical history, high resolution computed tomography and bronchiectasis-related parameters and skin prick test. At both times T0 and T1 we collected the following data: asthma control test (ACT), asthma control questionnaire (ACQ), immunoglobulin E (IgE) level, blood count, fractional exhaled nitric oxide 50 (FeNO 50) and flow-volume spirometry. The study was retrospectively registered. Results: Our population had a mean age of 59.08 ± 11.09 and 50% were female. At T1, patients on LTRA therapy had a significantly lower FeNO value (33.03 ± 23.61 vs. 88.92 ± 77.96; p = 0.012). We assessed that the value of ΔFeNO (FeNO 50 T1 − FeNO 50 T0) and the number of unplanned specialist visits allowed a discrimination of 66.7% in the presence of LTRA therapy. We also verified how low FeNO values at time T1 were statistically significant predictors of LTRA therapy (ODD = 9.96 (0.94–0.99); p = 0.032). Conclusion: The presence of LTRA in therapy in a population of severe asthmatics with coexisting non-ASBPA bronchiectasis and non-cystic fibrosis, acting simultaneously on the T helper type 2 (TH2) pathway and probably on the neutrophilic component of bronchiectasis, would allow a further amplification of the beneficial effects of biological therapy, leading to a reduction in the number of unplanned visits to specialists.

show abstract

Section: Discussionsupporting

confidence: 86%

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

Quaranta

Dragonieri

Crimi

et al. 2022

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, whilst the efficacy of mepolizumab is well documented, real-life data from independent sources on its effectiveness are currently limited, although growing through case series and global cohorts [ 13 , 14 ]. Also, several single-centre real-life studies have shown evidence of the effectiveness of mepolizumab [ 15 – 18 ]. Moreover, the stringent selection criteria adopted by clinical trials in general and by monoclonal antibody development programs in severe asthma are highly restrictive [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study

Domingo

Díaz

Aparicio

et al. 2021

Drugs

View full text Add to dashboard Cite

Background The efficacy of mepolizumab is well documented in severe eosinophilic asthma (SEA), although the stringent selection criteria adopted by SEA clinical trials limits the generalizability of results. Objective Our study evaluated the effectiveness and safety of mepolizumab in patients with SEA in Spain. The primary efficacy endpoint was the change in the rate of clinically significant asthma exacerbations 12 months after starting mepolizumab compared to the baseline rate in the 12 months prior to treatment. Patients were stratified by baseline blood eosinophil counts. Methods We conducted a multicentric observational cohort study of SEA patients treated with mepolizumab across 24 specialized hospital asthma units in Spain. Severe exacerbation rate, lung function, oral corticosteroid use (OCS) and asthma control test (ACT) were retrospectively collected and compared during the 12-month pre-and post-mepolizumab treatment. Adverse events were also investigated. Results A total of 318 patients with SEA were included (mean age: 56.6 years, 69.2% female). Exacerbation rates decreased by 77.5%, and 50.6% of patients did not suffer any exacerbations during the 12 months of treatment. The difference in forced expiratory volume in 1 s (FEV1) pre-and post-bronchodilator after starting mepolizumab was 0.21 (0.46) L (95% CI 0.14-0.27) (p < 0.001). Exacerbations and lung function significantly improved across all eosinophil subgroups. Among the 98 patients on OCS, 47.8% were able to discontinue this treatment and the mean daily dose was decreased by 59.9%. The baseline ACT score was 14.1, increasing by a mean (SD) of 6.7 points (1.9) at 12 months. Adverse events related to mepolizumab were uncommon. Conclusions This real-world study of SEA patients confirms that mepolizumab is effective in reducing clinically meaningful exacerbations, improving lung function, and decreasing OCS dependence and mean OCS dose at 12 months, irrespective of baseline eosinophil counts.The members of "on behalf of the REDES Study group" is present in the Acknowledgements section.

show abstract

“…The precise effects of anti-IL5/IL5R antibodies on FeNO remain unknown since this outcome was not included in phase 3 studies. However, a prospective real-life study on Benralizumab (J-BEST), 19 a retrospective study on anti-IL5 therapies by Ramonell et al 20 and a real-world settings study on Mepolizumab 21 reported no significant change in FeNO despite a significant reduction in blood eosinophils 19 , 21 and significant clinical benefits from the therapy. 19–21 These suggest that the therapeutic effect of anti-IL5/IL5R does not correlate with FeNO levels.…”

Section: Discussionmentioning

confidence: 99%

Increase in FeNO Levels Following IL5/IL5R-Targeting Therapies in Severe Asthma: A Case Series

Pelletier¹,

Godbout²,

Boulay³

et al. 2022

JAA

View full text Add to dashboard Cite

Purpose Monoclonal antibodies targeting interleukin-5 (IL5) and its receptor (IL5R), used for severe asthma treatment, reduce eosinophils to almost complete depletion. Fractional exhaled nitric oxide (FeNO), a surrogate marker of eosinophilic airway inflammation, is expected to decrease after their initiation. Our center noticed increased FeNO levels in a few patients in whom anti-IL5/IL5R therapy was initiated. Limited data are available on the kinetics of T2 inflammation biomarkers after initiation of a biologic in that population. This study aims to identify if a subgroup of severe asthma patients experiences increased FeNO levels after initiation of anti-IL5/IL5R therapy and to describe their clinical characteristics. Patients and Methods This is a retrospective case series of 5 patients on Benralizumab (4M:1F) and 8 on Mepolizumab (5M:3F) who showed a significant increase in FeNO (>20% AND >25 ppb) following initiation of an anti-IL5/IL5R treatment. Clinical data, expiratory flows, and inflammation were extracted from the patients’ chart at initiation of treatment (T 0 ), 3 months (T 1 ) and 12 months (T 2 ) post-treatment. Descriptive statistics were used. Results In patients treated with Benralizumab, the increase in FeNO was observed between T 0 and T 1 (mean delta = 82 ± 72 ppb) with a subsequent decrease (N = 3). In most patients taking Mepolizumab (N = 6), the FeNO increase was observed between T 1 and T 2 (mean delta = 57 ± 35 ppb). Under treatment, no Benralizumab patient experienced asthma exacerbation while two on Mepolizumab did. All patients had a significant decrease in blood eosinophils. Conclusion Although initiation of anti-IL5/IL5R may cause a transient rise in FeNO levels in a subgroup of patients, it does not appear to affect clinical outcomes. A compensatory mechanism involving other inflammatory pathways such as IL13 or IL4, both involved in FeNO production, could theoretically explain these findings. Further investigation is needed to elucidate the actual underlying mechanisms.

show abstract

Mepolizumab effectiveness in patients with severe eosinophilic asthma and co-presence of bronchiectasis: A real-world retrospective pilot study

Abstract: doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Cited by 42 publications

References 52 publications

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study

Increase in FeNO Levels Following IL5/IL5R-Targeting Therapies in Severe Asthma: A Case Series

Contact Info

Product

Resources

About