BackgroundPatients 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.MethodsData 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.ResultsWe 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 forced expiratory volume in 1 s percentage predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose and nasal polyps in Group 2; with Group 3 as the reference.ConclusionsTreatment response to mepolizumab in severe eosinophilic asthma follows three trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.

BACKGROUND:Asthma remission is a potential treatment goal. RESEARCH QUESTION:Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS:This secondary analysis used data from the Asthma and Macrolides: the Azithromycin Efficacy and Safety (AMAZES) clinical trial-a double-anonymized placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥ 80% or postbronchodilator FEV1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. RESULTS:A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION:In this study, adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

BACKGROUND:Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA). OBJECTIVE:To find whether early response to mepolizumab (100 mg) could predict future asthma remission and to identify the best predictor of treatment response to mepolizumab for achieving remission. METHODS:The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the 5-item Asthma Control Questionnaire (ACQ-5), oral corticosteroid (OCS) dose, exacerbation frequency, and postbronchodilator FEV1. Clinical remission, assessed at 12 months, was defined as an ACQ-5 score less than or equal to 1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve for internal validation. RESULTS:We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and postbronchodilator FEV1 at 6 months was more predictive of achieving remission than measures at 3 months. The ACQ-5 score at 6 months had the highest optimism-corrected area under the curve of 0.778 (95% CI, 0.719-0.833). An ACQ-5 score less than 1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, whereas an ACQ-5 score less than 0.75 had a specificity of 84.7%. CONCLUSIONS:The ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, in which treatment response is assessed at 6 months to predict clinical remission.

BACKGROUND:Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS:This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS:29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION:Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

BACKGROUND: 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.OBJECTIVE: 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. METHODS: 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. RESULTS: 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/mL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype.CONCLUSIONS: 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. (c) 2023 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:885-95)

Background: Asthma remission is a potential treatment goal. Objective: To evaluate the efficacy of two biologics (mepolizumab/omalizumab) and azithromycin in achieving remission in severe asthma patients. Methods: 788 patients (41% male; mean age 56.9±14.5 years) from three severe asthma datasets (the Australian Mepolizumab Registry [AMR], the Australian Xolair Registry [AXR], and the AMAZES RCT) were included in the analysis. Each dataset was analysed separately. Three definitions of remission were explored: 1) symptom remission (no exacerbations and no OCS use during the previous six months plus ACQ-5≤1 at 12 months; 2) clinical remission (symptom remission plus FEV1≥80% at 12 months); and 3) complete remission (clinical remission plus blood eosinophil count≤300 cells/microliter at 12 months). The predictors of clinical remission were identified using logistic-regression analysis. Results: Among AMR patients, 29.3% achieved symptom remission and 8.9% achieved both clinical and complete remission. Among AXR patients, 22.8% achieved symptom and 5.2% achieved clinical remission. AMAZES patients had lower baseline disease severity, and 50.6%, 27.2% and 19.9% achieved symptom, clinical and complete remission, respectively. Better lung function, better asthma-related QoL and absence of OCS burst at baseline predicted the odds of achieving clinical remission. Conclusion: Twelve months treatment with add-on therapies, mepolizumab, omalizumab or azithromycin, induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target in severe asthma and future studies should consider remission as an outcome measure.

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. In clinical practice, mepolizumab reduces the burden of severe eosinophilic asthma by reducing severe exacerbations and improving asthma control, quality of life and lung function. Super-responders have a T2 phenotype and few comorbidities. http://bit.ly/2UIio4x