Mepolizumab In Severe Eosinophilic Asthma Research Articles

Distinct trajectories of treatment response to mepolizumab toward remission in patients with severe eosinophilic asthma.

Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6, and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations, and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.We identified three trajectory groups: group 1, responsive asthma with less OCS use (n=170); group 2, responsive late-onset asthma (n=58); and group 3, obstructed and less responsive asthma (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to group 3 with 5.7% (p <0.001). Baseline predictors for assigned groups included lower OCS dose in group 1; greater FEV1% predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose, and nasal polyps in group 2; with group 3 as the reference.Treatment response to mepolizumab in severe eosinophilic asthma follows 3 trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.

Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma

BackgroundMepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. ObjectiveOur study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. MethodThe MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA. ResultsIn patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated.Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. ConclusionAt stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.

Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China

Objective To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. Methods A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. Results Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. Conclusion Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Can we predict who will benefit most from biologics in severe asthma? A post-hoc analysis of two phase 3 trials

BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87‒0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02‒0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03‒2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19‒0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16‒0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much from therapy. Patient characteristics had a greater capacity to predict treatment response to asthma control than to exacerbation.Trial registrationClinicalTrials.gov number, NCT01691521 (registered September 24, 2012) and NCT01000506 (registered October 23, 2009).

Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma

Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. Patients enrolled in the Australian Mepolizumab Registry (n= 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Mepolizumab prefilled syringe for the treatment of severe eosinophilic asthma: focus on the pediatric population

Introduction Eosinophil-targeted therapy with mepolizumab for severe eosinophilic asthma has significantly improved asthma control and patient quality of life, though administration in children had been restricted to healthcare provider reconstitution of a lyophilized powder into a solution with in-clinic administration until recently. Here, we profile the newly FDA-approved use of mepolizumab as a prefilled syringe for the treatment of severe eosinophilic asthma in children aged 6 – 11 years old, allowing for home administration. Areas covered A literature search was conducted on PubMed using keywords such as mepolizumab, severe asthma, eosinophils, IL-5, anti-IL-5, children, pediatric, prefilled syringe, and home administration in several combinations. Published literature through July, 2022 including clinical trials and prescribing information for mepolizumab for severe eosinophilic asthma, particularly for use in children and as administration as a prefilled syringe is reviewed. Expert opinion Asthma affects a significant number of children worldwide, and having efficacious tolerable targeted precision therapies for this population is crucial. Mepolizumab remains the only targeted anti-IL-5 therapy approved for pediatric asthma down to 6 years of age. The innovation of the prefilled syringe will enable home administration, which would decrease the burden of treatment, and could potentially increase adoption of therapy.

Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma—A Randomized, Placebo-Controlled Crossover Trial (MAPLE)

Mepolizumab inhibits IL-5 activity and reducesexacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma(SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms. To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment. A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo,-0.23; 95% CI,-0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI,-0.26 to 0.42), St. George's Respiratory Questionnaire (0.24; 95% CI,-3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI,-0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI,-4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%). OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.

Long-term safety and effectiveness of mepolizumab for severe eosinophilic asthma

Severe Asthma is a limiting condition that can be challenging to manage Biologicals represent a safe and efficient alternative to treat this disorder, but studies on their long-term effectiveness and safety are scarce.Severe Asthma is a limiting condition that can be challenging to manage Biologicals represent a safe and efficient alternative to treat this disorder, but studies on their long-term effectiveness and safety are scarce.

Oral corticosteroid-sparing effects of mepolizumab in severe eosinophilic asthma: evidence from randomized controlled trials and real-world studies.

Oral corticosteroids (OCS) have long been a mainstay of treatment for asthma exacerbations and chronic severe asthma. However, it is increasingly recognized that both long-term and short-term OCS use are directly associated with a wide range of serious adverse effects, and as such OCS-sparing treatment alternatives are now widely recommended for patients with severe asthma. While several international guidelines recommend these treatments, guidance on OCS tapering, and which patients are most likely to tolerate OCS reduction and/or discontinuation, is still lacking. Several biologics have demonstrated efficacy in patients with OCS-dependent asthma. One OCS-sparing treatment is the anti-interleukin-5 monoclonal antibody mepolizumab, which is approved for the treatment of severe eosinophilic asthma. In addition to improved exacerbation rates, asthma control, quality of life, and lung function among patients with severe eosinophilic asthma, mepolizumab also has an OCS-sparing effect, which has been demonstrated in randomized controlled trials and real-world studies. Both physicians and patients express concerns about the adverse effects of OCS, and additional data from the randomized, controlled SIRIUS trial (NCT01691508) highlight the high level of concern among patients regarding OCS-related burden. In this article, we discuss current guidance on OCS-sparing strategies for patients with severe asthma, provide a summary of the available evidence of the OCS-sparing effect of mepolizumab, and highlight patient and physician perspectives on the use of OCS and OCS-sparing treatments in severe asthma.

Health outcomes after stopping long-term mepolizumab in severe eosinophilic asthma: COMET.

Asthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic asthma. This analysis of COMET evaluated whether stopping versus continuing long-term mepolizumab therapy impacted these outcomes.Patients with severe eosinophilic asthma with ≥3 years continuous mepolizumab treatment (via COLUMBA (NCT01691859) or COSMEX (NCT02135692) open-label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study. Patients were randomised 1:1 to continue mepolizumab 100 mg subcutaneous every 4 weeks or to stop mepolizumab, plus standard of care asthma treatment. Patients could switch to open-label mepolizumab following an exacerbation. Health outcome endpoints included time to first asthma worsening (composite endpoint: rescue use, symptoms, awakening at night and morning peak expiratory flow (PEF)), patient and clinician assessed global rating of asthma severity and overall perception of response to therapy, and unscheduled healthcare resource utilisation.Patients who stopped mepolizumab showed increased risk of and shorter time to first asthma worsening compared with those who continued mepolizumab (hazard ratio (HR) 1.71; 95% CI 1.17–2.52; p=0.006), including reduced asthma control (increased risk of first worsening in rescue use (HR 1.36; 95% CI 1.00–1.84; p=0.047) and morning PEF (HR 1.77; 95% CI 1.21–2.59; p=0.003). There was a higher probability of any unscheduled healthcare resource use (HR 1.81; 95% CI 1.31–2.49; p<0.001), and patients and clinicians reported greater asthma severity and less favourable perceived response to therapy for patients who stopped versus continued mepolizumab.These data suggest that patients with severe eosinophilic asthma continuing long-term mepolizumab treatment sustain clinically important improvements in health outcomes.

Prospective Italian real-world study of mepolizumab in severe eosinophilic asthma validates retrospective outcome reports.

Prospective Italian real-world study of mepolizumab in severe eosinophilic asthma validates retrospective outcome reports.

Real-world Effectiveness of Mepolizumab in Severe Eosinophilic Asthma: A Systematic Review and Meta-analysis

PurposeMepolizumab is a human monoclonal antibody against interleukin 5 (IL-5) used to treat severe eosinophilic asthma. Several studies have evaluated the effectiveness of mepolizumab in the real world. We conducted a systematic review and meta-analysis in the context of heterogeneity among patients, clinicians, and treatment regimens to study the effectiveness of mepolizumab in the real world. MethodsWe searched the PubMed and Embase databases for real-world studies on severe asthma treatment with mepolizumab as of June 30, 2020. Exacerbations, asthma-related hospitalizations, forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) or Asthma Control Test (ACT), corticosteroid use, peripheral blood eosinophil counts, and the fraction of exhaled nitric oxide were selected as indicators to evaluate the effectiveness. Standardized mean differences by the Cohen method and mean differences were chosen as indicators of effect size. Cohen d values of 0.2, 0.5, and 0.8 are considered as small, medium, and large effects, respectively. We used the Dersimonian-Laird random-effect model to quantify pooled effectiveness estimates. FindingsA total of 1457 patients from 13 studies were included in this review. At all time points, mepolizumab was associated with reductions in exacerbations (2.92 and 2.73 events per patient per year fewer at 6 and 12 months, respectively) and hospitalizations (0.36 events per patient per year fewer at 12 months); improvements in asthma control (ACQ scores reductions of 1.32 and 1.03 at 6 and 12 months, respectively; ACT scores increase of 6.52 at 6–12 months); slight improvements in pulmonary function (FEV1 increase of 0.23 L at 1–3 months and 6–12 months, respectively); reductions in oral corticosteroid use (9.02- and 7.68-mg decrease at 6 and 12 months, respectively); and reductions in peripheral blood eosinophil counts (decreases of 559.11 cells/μL and 599.17 cells/μL at 1–3 months and 6–12 months, respectively) and fraction of exhaled nitric oxide (13-ppb reduction at 6–12 months). ImplicationsOur study suggests that mepolizumab is associated with improvements in several clinically meaningful real-world outcomes. This study is a supplement to and extension of the efficacy of randomized controlled trials of mepolizumab.

Mepolizumab in severe eosinophilic asthma reduces healthcare use

Mepolizumab in severe eosinophilic asthma reduces healthcare use

Real-World Effectiveness and the Characteristics of a “Super-Responder” to Mepolizumab in Severe Eosinophilic Asthma

Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. How do patients with severe eosinophilic asthma respond to mepolizumab in the real world setting and which characteristics are associated with a super-response to this therapy? We conducted a retrospective review of all patients who received at least 16weeks of treatment with mepolizumab (100mg subcutaneously) for SEA at our regional asthma center in the United Kingdom. Clinical data were collected at each 4-week visit. At 16, 24, and 52weeks, patients were classified as "responders" or "nonresponders." A response was defined as≥50%reduction in exacerbations; for patients whose condition requires maintenance oral corticosteroids (mOCS), a response was defined as≥50%reduction in prednisolone dose. Super responders were defined as exacerbation-free and off mOCS at one year. Ninety-nine patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04 ± 2.57 to 1.86 ± 2.17 per year at one year (54%reduction; P< .001). Sixty-eight patients were receiving mOCS at the time of commencing mepolizumab. By one year, the daily median dose fell from 10mg (interquartile range, 10 to 15) to 0mg (interquartile range, 0 to 10; P< .001). Fifty-seven percent of them were able to discontinue mOCS; 72.7%(95%CI, 63.0 to 80.7) of the patients were classified as responders, and 28.3%(95%CI, 20.2 to 38.0) of the patients were classified as super responders. Baseline characteristics associated with responder and super responder status included the presence of nasal polyposis (P= .012), lower baseline Asthma Control Questionnaire 6 (P= .006), a lower BMI (P= .014), and, in those patients receiving mOCS, a significantly lower prednisolone dose at baseline (P= .005). At 16weeks, the one-year responder status was correctly identified in 80.8%patients; by 24weeks, this status rose to 92.9%. In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90%of patients by week24.

Mepolizumab effectiveness and identification of super-responders in severe 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.

Efficacy of long-term treatment with mepolizumab in severe eosinophilic asthma (case reports)

Two clinical cases of severe eosinophilic asthma taking long-term therapy with mepolizumab (38 and 45 months are described in the article. Both the cases demonstrate the effectiveness of the drug both in allergic and non-allergic (aspirin-induced) asthma. Significant clinical improvement was achieved in both cases under the treatment with mepolizumab during ≥ 3 years. Important results of the treatment were improvement in symptoms of severe asthma, reduction in exacerbation rate, and, additionally, overcoming corticosteroid addiction in patients. The therapy with mepolizumab was highly safe.

Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma.

Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes. This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks. This meta-analysis reports data from patients receiving the licensed dose of mepolizumab (100 mg SC) or placebo only. The primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints included rate of exacerbations requiring hospitalization/emergency room (ER) visit, proportion of patients with no clinically significant exacerbations, and changes from baseline in forced expiratory volume in 1 s, Asthma Control Questionnaire-5 and St George's Respiratory Questionnaire scores. Analyses were stratified by baseline blood eosinophil count (<150, ≥150, ≥300, ≥400, ≥500, ≥750, ≥1000, ≥150-<300, or ≥300-<500 cells/μL). Mepolizumab reduced annual clinically significant exacerbation rates by 45%-85%, exacerbations requiring hospitalization/ER visit by 60%-70%, and increased the odds of no clinically significant exacerbations across all eosinophil threshold subgroups versus placebo, and improved all other secondary endpoints in subgroups ≥150 cells/μL. Greater treatment effects with increasing blood eosinophil count were observed. Mepolizumab demonstrated consistent clinical benefits in patients with baseline blood eosinophil counts ≥150 cells/μL, confirming the suitability of this cut-off for identifying patients responsive to the licensed mepolizumab dose.

Эффективность и безопасность меполизумаба при тяжелой эозинофильной астме: обзор литературы

Эффективность и безопасность меполизумаба при тяжелой эозинофильной астме: обзор литературы

Mepolizumab for severe eosinophilic asthma: a real-world snapshot on clinical markers and timing of response

ABSTRACTBackground: Few studies have provided real-world evidence of mepolizumab efficacy and safety. We aimed to evaluate mepolizumab for severe eosinophilic asthma in daily clinical practice.Research design and methods: Patients included in the RINOVA (Interdisciplinary Network for the management of severe asthma in Veneto region, Italy) database were investigated. Blood eosinophil count, forced expiratory volume in 1 second, % of predicted (FEV1%), fractional exhaled nitric oxide (FeNO), asthma control test (ACT), oral steroid (OCS) intake, and exacerbation rate were evaluated during mepolizumab treatment.Results: 69 patients were enrolled (mean age: 55.1 years; 60.9% females). A significant improvement was detected at one month with respect to blood eosinophils (median level at baseline: 710/μl; −620/μl, p < 0,001), FEV1% (median value at baseline 87; range: 79–101; +4, p = 0.001) and ACT (median value at baseline 18; range: 14–20.5;+4, <0.001). A significant reduction of FeNO was observed six months after the treatment start, when the exacerbation rate and the mean OCS dose significantly decreased (respectively: Δ reduction −3; p < 0.001 and −5 mg; p < 0.001).Conclusions: Our study provides real-world evidence of mepolizumab safety and confirms its dramatic steroid sparing effect. The greatest clinical change (ACT and FEV1) was observed within the first month.