Efficacy Of Mepolizumab Research Articles

A real-life comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2-biologics

BackgroundSevere asthma (SA) with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with type 2 (T2) inflammatory endotype. Consequently, therapeutic targets are T2 biologics. The present retrospective study aimed to analyze and compare the clinical efficacy of mepolizumab, benralizumab, omalizumab, and dupilumab in patients with SA and comorbid CRSwNP. Methods115 adult patients with SA and CRSwNP receiving 1 of the 4 biologics (mepolizumab n = 31; benralizumab n = 27; dupilumab n = 27; omalizumab n = 30) were included in the retrospective open monocentric study. Pulmonary and rhinological parameters were evaluated by Asthma Control Test (ACT), FEV1%, GINA-severity grade, rhinological questionnaires (CRS VAS-scores and sinonasal QoL RSOM-31) before and after 4–6 months of therapy. ResultsAfter 4–6 months of therapy, the Asthma Control Test and FEV1% significantly improved in all biologics groups (p < 0.01). GINA-score significantly improved in the omalizumab group only (p < 0.01). Overall, most nasal scores measured by VAS, total and nasal RSOM-31 subscores improved in all treatment groups (p < 0.05). Interestingly, the most significant differences in pre/post scores were observed in the patients receiving dupilumab, with the most notable improvement for all nasal symptoms, RSOM-31 total score, and RSOM-31 nasal subscore. There were no significant changes in the VAS scores loss of smell in the benralizumab group and postnasal drip in the mepolizumab group. ConclusionT2-targeting biologics effectively treat asthma in patients with severe asthma and comorbid CRSwNP. However, the efficacy of T2 biologics differs regarding the outcome in CRSwNP.

Real-life efficacy and safety of mepolizumab for eosinophilic granulomatosis with polyangiitis

• Mepolizumab (MPZ), an anti-IL5 monoclonal antibody, is a promising treatment for eosinophilic manifestations in eosinophilic granulomatosis with polyangiitis (EGPA). • Little is known on safety and efficacy of MPZ in EGPA in real-life. • This study provides evidence supporting routine use of MPZ use as a safe and effective treatment for refractory eosinophilic manifestations in patients with EGPA. • An apparent rise in minor infections during MPZ treatment warrants further studies. Little is known about the efficacy and safety of the anti-interleukin 5 monoclonal antibody mepolizumab (MPZ) in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in real-life. We thus evaluated disease activity, damage and disease-related complications in 14 patients with EGPA receiving MPZ for refractory disease for a median time of 16 months in comparison with up to five years before MPZ start. Asthma exacerbation rates, the Birmingham Vasculitis Activity Score and corticosteroid dosage decreased during MPZ ( p < 0.001, p < 0.001 and p = 0.001, respectively). Five patients could discontinue prednisone. Infection rates were higher during MPZ ( p < 10 –6 ), but no rises in hospitalizations, asthma exacerbations or damage accrual were observed. Real-life data confirm the effectiveness of MPZ in refractory EGPA with active asthma. Higher infections rates are in line with other studies and might be due to relative overreporting secondary to increased visit frequency, although a pharmacological effect could not be ruled out.

REAL WORLD EFFECTIVENESS OF MEPOLIZUMAB IN PATIENTS WITH ALLERGIC AND NON-ALLERGIC ASTHMA

<h3>Introduction</h3> Eosinophilia provides a common denominator for overlapping allergic and non-allergic asthma phenotypes and offers a basis for the efficacy of mepolizumab. While efficacy and safety of mepolizumab in severe asthma is well-documented, comparative effectiveness data among allergic and non-allergic phenotypes is limited. This study compared the impact of treatment with mepolizumab on patients with allergic versus non-allergic asthma. <h3>Methods</h3> This was a retrospective cohort study using administrative claims data from Optum Research Database. The study population included patients with asthma (>=6 years) initiated on mepolizumab between January 2016–December 2019. The asthma exacerbation rate and OCS use were assessed in both the 12 months before (baseline period) and 12 months following (follow-up period) mepolizumab initiation. Allergic status was ascertained using diagnosis codes, medication use and lab test results. <h3>Results</h3> In total 240 (44.6%) allergic and 298 (55.4%) non-allergic asthma patients met eligibility criteria. The mean (SD) asthma exacerbation rate was substantially reduced from baseline to follow-up for both allergic asthma (3.19[2.49] to 2.10[2.12], p<0.001) and non-allergic asthma patients (2.51[2.17] to 1.70[1.92], p<0.001). Significant reduction was also observed with regards to mean (SD) count of OCS claims from baseline to follow-up for patients with allergic (5.19[4.47] to 3.46[4.50], p<0.001) and non-allergic asthma (5.46[4.12] to 3.20[3.69], p<0.001). No significant differences were observed between cohorts in the decreases in asthma exacerbations or counts of OCS claims from baseline to follow-up. <h3>Conclusion</h3> This study supports the real-world effectiveness of mepolizumab for the treatment of severe asthma with allergic and non-allergic phenotypes.

Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis

The comparative safety and efficacy of the biologics currently approved for asthma are unclear. We compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma. We performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma. Eight randomized clinical trials (n= 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV1: dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, -0.63; 95% CI, -0.81 to -0.45), dupilumab (MD, -0.48; 95% CI, -0.83 to -0.14), and benralizumab (MD, -0.32; 95% CI, -0.43 to -0.21). In individuals with eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV1. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4). There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma.

Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5

Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P= .76 and P= .90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P= .42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.

Efficacy of anti-IL-5 therapy with mepolizumab for severe bronchial asthma and concomitant inflammatory nasal diseases in real clinical practice

BACKGROUND. T2 inflammation underlies non-allergic eosinophilic severe bronchial asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Existing targeted anti-IL-5 drugs can improve clinical and functional parameters in patients with a combination of severe asthma and CRSwNP.&#x0D; AIM: to evaluate mepolizumab efficacy in patients with non-allergic severe asthma and concomitant inflammatory nasal diseases (CIND) in real clinical practice.&#x0D; MATERIALS AND METHODS. The study was conducted without a control group, by comparing related populations (before-after analysis) and based on the Sverdlovsk regional register of adult patients with severe asthma and CIND. The primary endpoint was asthma control achievement (ACT questionnaire) and decrease in the proportion of patients with uncontrolled severe asthma. The number of asthma exacerbations, emergency calls and hospitalizations, quality of life according to AQLQ questionnaire, peripheral blood eosinophils level and respiratory function (FEV1, FVC, FEV1/FVC) were also assessed. Dynamics of nasal symptoms was assessed using SNOT22 questionnaire and visual analogue scale (VAS).&#x0D; RESULTS. During 12 months of therapy with mepolizumab, ACT increased from 9 (Q1-Q3: 7-11) to 22 points (Q1-Q3: 21-24) (p0.001). The proportion of patients with uncontrolled asthma decreased from 100% to 10% (p0.001). The number of asthma exacerbations decreased from 3.182.8 per patient per year to 0 (p0.001) and hospitalizations from 0.570.9 per patient per year to 0 (p=0.007). Quality of life according to AQLQ increased from 3.481.05 (95% CI 2.734.24) to 5.590.88 (95% CI 4.966.22) points (p0.001). The number of blood eosinophils decreased from 442 (Q1-Q3: 336-853) to 90 (Q1-Q3: 73-117) cells/l (p0.001). There was increase in FEV1 from 63.9%24.2 (95% CI 46.681.2) to 80.5%18.3 (95% CI 67.493.6) (p=0.015). There was decrease in SNOT22 questionnaire score by 33 points (from 4530 to 2215) (p=0.006) and decrease in VAS score by 5 points (from 8 (Q1-Q3: 5-8) to 3 (Q1-Q3: 3-5)) (p=0.017).&#x0D; CONCLUSIONS. According to the study results, there were asthma control improvement, asthma exacerbations decrease, quality of life improvement according to AQLQ. Statistically significant peripheral blood eosinophils decrease and respiratory function improvement were also revealed. In patients with CIND, significant improvement in nasal breathing was noted, which was confirmed by scores of SNOT22 and VAS questionnaires.

Safety and efficacy of mepolizumab at home admnistration- a portuguese experience

Safety and efficacy of mepolizumab at home admnistration- a portuguese experience

Clinical and Lung Function Outcomes After Anti-IgE or Anti-IL5 Therapy in Severe Asthma.

BackgroundAlthough there have been indirect comparisons of the relative efficacy of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in severe asthma patients, long-term direct head-to-head comparisons are lacking. Here, we (i) examined the effect of mepolizumab, benralizumab, and omalizumab on symptom control and lung function parameters over time; and (ii) compared the efficacy of mepolizumab and benralizumab on symptom control and lung function outcomes.MethodsThis was a retrospective study of patients with severe asthma taking anti-IgE (omalizumab; n = 24), anti-IL5 (mepolizumab, n = 23), or anti-IL-Rα (benralizumab; n = 12) therapy. Data were extracted on (i) Asthma Control Questionnaire (ACQ-5) scores; (ii) forced expiratory volume over 1 second (FEV1); and (iii) peak expiratory flow rate (PEFR) at 4–6 months and 1 year and documented reductions in exacerbations. Clinical and lung function outcomes were compared between patients taking mepolizumab and benralizumab and over time.ResultsThere were significant decreases in ACQ-5 scores (3.3 ± 0.93 to 1.7 ± 0.98 for mepolizumab, 3.5 ± 0.72 to 1.6 ±0.89 for benralizumab, and 3.5 ± 0.95 to 1.7 ± 1.1 for omalizumab; t-test, all p < 0.0001) but not increases in FEV1 and PEFR for all three agents after 4–6 months of therapy, which persisted but did not decrease further at one year. There were trends toward a greater percentage increase in FEV1 and PEFR from baseline and a decrease in the number of exacerbations in patients taking benralizumab than those taking mepolizumab.ConclusionAlthough limited by a small sample size, this real-world, head-to-head comparison of mepolizumab and benralizumab is consistent with comparative data on asthma biologicals and indirect comparisons showing no major difference in efficacy. The study also generates new testable hypotheses about the efficacy of asthma biologicals in different patient populations.

Impact of Baseline Treatment, Duration of Disease, and Refractory Status on Outcomes in Mepolizumab-Treated Patients With EGPA

Mepolizumab, an anti-interleukin-5 monoclonal antibody has been shown to increase remission duration in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We investigated impact of baseline treatment, disease duration, and refractory status on mepolizumab efficacy using Phase III MIRRA study data.

Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count

In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP. We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC). SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory. Analyses included 407 patients (289 with asthma; 108with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/μL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/μL: 55.0% vs 31.3%; ≥150 cells/μL: 49.5% vs 28.1%; <300 cells/μL: 50.7% vs 29.0%; ≥300 cells/μL: 50.4% vs 28.1%). Asimilar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups. Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Efficacy of mepolizumab in usual clinical practice and characteristics of responders

BackgroundSevere eosinophilic asthma is a high-burden disease. Mepolizumab has been effective in several randomized clinical trials. However, such success might not be applicable to patients treated in usual clinical practice. The objectives of this article are to evaluate the efficacy of mepolizumab in severe uncontrolled eosinophilic asthma under usual clinical practice, and to determine characteristics associated with the response to this treatment. MethodsWe have conducted a retrospective, multicentre study, including all adult patients with severe uncontrolled eosinophilic asthma in Galicia, Spain, on whom mepolizumab treatment was started before June 2020, at least 6 months before the time of inclusion, and had received at least one dose of the drug. Patient characteristics, clinical data, respiratory function and comorbidities were collected at baseline and at the 6-month-follow-up. Responders and super-responders were defined according to clinical response and requirement of systemic corticosteroids. Results122 patients (mean age 58 years old) were included. In the follow-up treatment 6 months later, 75.4% of the patients were well-controlled, displaying a significant reduction in blood eosinophil counts (p < 0.001), hospital admissions and disease exacerbations (p < 0.001), and had their systemic glucocorticosteroid dose significantly reduced (p < 0.001). The inhaled corticosteroid dose was also lowered (p < 0.01) after 6 months of treatment. Around two-thirds had a clinically significant increase in FEV1, 95% of the patients were considered responders and 43% super-responders. ConclusionIn routine clinical practice, mepolizumab is effective in patients with severe eosinophilic asthma and it has a good safety profile.

Effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, steroid dependence, and small airways in patients with severe eosinophilic asthma

Background/aim The efficacy of mepolizumab has been largely demonstrated in clinical trials in patients with severe eosinophilic asthma (SEA). However, reports on experience with mepolizumab in a real-life cohort are limited. Moreover, data about the effectiveness of mepolizumab on small airways is scarce. This study evaluated the effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, blood eosinophils, steroid dependence, and small airways in a real-life cohort of patients with SEA.Materials and methodsWe retrospectively analyzed patients with SEA who were receiving fixed-dose mepolizumab. The effects of mepolizumab on clinical, laboratory, functional parameters were evaluated at 12th, 24th, and 52nd weeks. Small airways were assessed with the FEF 25-75.Results A total of 41 patients were enrolled in the study. Mepolizumab significantly reduced asthma exacerbation rates, reduced mOCS dose, and improved asthma control test (ACT) scores at 12th, 24th, and 52nd weeks. However, we found no significant changes in FEV1 and FEF25-75 values at baseline, 12th, 24th, and 52nd weeks (78.9 ± 23.3%, 82.9 ± 23.4%, 81.9 ± 23.9%, and 78.9 ± 23.5% for FEV1; 45.1 ± 23.1%, 48.8 ± 23.5%, 48.7 ± 23.1%, and 41.0 ± 20.1% for FEF25-75, respectively)Conclusion In this study, mepolizumab significantly improved all outcomes (symptom scores, asthma exacerbations, OCS sparing, and blood eosinophils) except functional parameters. Still, despite the dose reduction in mOCS dosage, no significant deterioration was observed in FEV1 and FEF25-75 values.

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study

A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α-negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. Of 104 patients who completed the double-blind study, 98% (previous placebo, n= 52; previous mepolizumab, n= 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n= 14; previous mepolizumab, n= 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. Extended mepolizumab treatment was associated with a positive benefit-risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α-negative HES.

Improving analysis practice of continuous adverse event outcomes in randomised controlled trials - a distributional approach

BackgroundRandomised controlled trials (RCTs) provide valuable information for developing harm profiles but current analysis practices to detect between-group differences are suboptimal. Drug trials routinely screen continuous clinical and biological data to monitor participant harm. These outcomes are regularly dichotomised into abnormal/normal values for analysis. Despite the simplicity gained for clinical interpretation, it is well established that dichotomising outcomes results in a considerable reduction in information and thus statistical power. We propose an automated procedure for the routine implementation of the distributional method for the dichotomisation of continuous outcomes proposed by Peacock and Sauzet, which retains the precision of the comparison of means.MethodsWe explored the use of a distributional approach to compare differences in proportions based on the comparison of means which retains the power of the latter. We applied this approach to the screening of clinical and biological data as a means to detect ‘signals’ for potential adverse drug reactions (ADRs). Signals can then be followed-up in further confirmatory studies. Three distributional methods suitable for different types of distributions are described. We propose the use of an automated approach using the observed data to select the most appropriate distribution as an analysis strategy in a RCT setting for multiple continuous outcomes. We illustrate this approach using data from three RCTs assessing the efficacy of mepolizumab in asthma or COPD. Published reference ranges were used to define the proportions of participants with abnormal values for a subset of 10 blood tests. The between-group distributional and empirical differences in proportions were estimated for each blood test and compared.ResultsWithin trials, the distributions varied across the 10 outcomes demonstrating value in a practical approach to selecting the distributional method in the context of multiple adverse event outcomes. Across trials, there were three outcomes where the method chosen by the automated procedure varied for the same outcome. The distributional approach identified three signals (eosinophils, haematocrit, and haemoglobin) compared to only one when using the Fisher’s exact test (eosinophils) and two identified by use of the 95% confidence interval for the difference in proportions (eosinophils and potassium).ConclusionWhen dichotomisation of continuous adverse event outcomes aids clinical interpretation, we advocate use of a distributional approach to retain statistical power. Methods are now easy to implement. Retaining information is especially valuable in the context of the analysis of adverse events in RCTs. The routine implementation of this automated approach requires further evaluation.

Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials

BackgroundSevere asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma.MethodsThis was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies. Patients aged ≥ 12 years with severe eosinophilic asthma and a history of exacerbations were randomised to receive placebo (MENSA/MUSCA), mepolizumab 75 mg intravenously (MENSA) or 100 mg subcutaneously (SC) (MENSA/MUSCA) every 4 weeks for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations and changes from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1), St George’s Respiratory Questionnaire (SGRQ) total score and Asthma Control Questionnaire (ACQ)-5 score. Analyses were performed by baseline age of asthma onset (< 18 years; 18–40 years; ≥ 40 years); lung function (% predicted FEV1 ≤ 60; 60–80; > 80); airway reversibility (reversible [≥ 12% change in FEV1]; non-reversible [< 12% change in FEV1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score ≥ 1.5]; partial/complete control [ACQ-5 score < 1.5]).ResultsOverall, 936 patients received mepolizumab 100 mg SC or placebo. Across age at asthma onset, lung function and airway reversibility subgroups, mepolizumab reduced the rate of clinically significant exacerbations by 49–63% versus placebo. Improvements in lung function, SGRQ total score and ACQ-5 score were also seen with mepolizumab versus placebo across most age and lung function subgroups. Clinically significant exacerbations were reduced with mepolizumab versus placebo irrespective of season or allergen sensitivity; SGRQ total and ACQ-5 scores were generally improved across seasons.ConclusionsMepolizumab efficacy was consistent for patients with varying age at asthma onset, lung function, airway reversibility and allergen sensitivities at baseline. Our results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma with a broad range of baseline clinical characteristics; large-scale real-world studies are needed to confirm the external validity of these findings.Trial registration Post hoc meta-analysis of data from MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862)

Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions

BackgroundComorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.MethodsThis was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline.ResultsOverall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup.ConclusionsMepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity.Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO.

BackgroundA pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses.MethodsIn METREX (117106/NCT02105948) and METREO (117113/NCT02105961), randomized patients received mepolizumab or placebo added to existing inhaled corticosteroid (ICS)–based triple maintenance therapy. The annual rate of moderate/severe exacerbations (primary endpoint) was compared between subcutaneous (SC) mepolizumab 100 mg versus placebo (primary comparison of interest) and all doses (100 mg and 300 mg SC) versus placebo in patients with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year. Secondary/other endpoints included time to first moderate/severe exacerbation, exacerbations leading to emergency department visit/hospitalization and health-related quality of life (HRQoL). A predictive model of the relationship between screening blood eosinophil counts and exacerbation rates included data from all randomized patients.ResultsIn total, 1510 patients were randomized in METREX and METREO and 1136 patients were included in the pre-specified meta-analysis. From the meta-analysis, mepolizumab 100 mg SC significantly reduced annual moderate/severe exacerbation rates versus placebo by 18% (rate ratio: 0.82; 95% confidence interval: 0.71, 0.95; p=0.006) and delayed time to first moderate/severe exacerbation (hazard ratio: 0.80 [0.68, 0.94]; p=0.006). Mepolizumab 100 mg SC versus placebo numerically reduced exacerbations leading to ED visits/hospitalization and improved HRQoL. A modelling approach demonstrated increasing efficacy for moderate/severe exacerbations with increasing screening blood eosinophil count; this relationship was more pronounced for exacerbations requiring oral corticosteroids (post hoc). The all-doses comparison had similar results.ConclusionMepolizumab reduces exacerbations in patients with eosinophil-associated COPD. Results suggest that blood eosinophil counts (≥150 cells/µL at screening or ≥300 cells/µL in the prior year) allow for identification of patients with COPD who experience exacerbations while treated with maximal ICS-based triple maintenance therapy who are likely to benefit from mepolizumab.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Efficacy of mepolizumab in elderly patients with severe asthma and overlapping COPD in real-world settings: A retrospective observational study.

Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory diseases, presenting overlapping prevalence with age. Mepolizumab is a humanized monoclonal antibody targeting interleukin-5. In major randomized clinical trials, this antibody reportedly reduced the circulating eosinophil count, exacerbation rate, and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data regarding the efficacy of mepolizumab in elderly patients with asthma and overlapping COPD are limited. This was a single-center, retrospective, observational study. Elderly patients (age ≥65 years) administered mepolizumab between August 2016 and March 2019 were enrolled and the effects of mepolizumab on the eosinophil level, exacerbation numbers, OCS dosage, and lung functions were assessed. We compared treatment responses in patients with asthma and COPD overlap (ACO) with responses observed in patients with severe asthma alone. Adverse events were also evaluated. Twenty patients (10 men and 10 women), with a mean age of 77.5±1.3 years, were included. Mepolizumab significantly reduced the blood eosinophil count, as well as significantly decreased clinically significant exacerbation, in both populations. The OCS dosage was significantly reduced in patients treated receiving maintenance OCS therapy. However, mepolizumab did not improve lung function in either population, and no significant difference was observed in treatment responses between patients with asthma alone and ACO. Mepolizumab may be effective in elderly patients with eosinophilic asthma and ACO.