Maintenance Oral Corticosteroids Research Articles

Difficult-to-treat asthma patients from ethnic minority groups in central England are at an enhanced risk of house dust mite sensitisation.

House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero-allergens. To compare the ethnicity-based patterns of sensitisation to aero-allergens and the impact of ethnicity on clinical outcomes in patients with difficult-to-treat asthma (DTA). Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity-based risk factors for HDM sensitisation. A total of 1272 patients [White 1016 (79.9%), EMG 256 (20.1%) EMG] with a median age of 51years (range 16-97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), p<0.0001. Positive HDM sensitisation was more prevalent in the EMG than in the White group [142/216 (66%) versus 375/842 (45%), p<0.0001]. The median HDM ssIgE level was higher in the EMG than in the White group [3.0 KUA/L (IQR 0.06, 11.5) versus 0.1 (0.01, 3.0), p<0.000001]. The odds ratio for positive sensitisation to HDM conveyed by the EMG status was 2.61 (95%CI, 1.8-3.8), p<0.0001. Compared to the White group, the EMG had higher median total serum IgE [326 KU/L (115, 971) versus 114 (29.8, 434.8), p<0.000001], higher blood eosinophil count (0.36×109 (0.18, 0.62) versus 0.23 (0.1,0.47), p<0.000001), were marginally more atopic (79.2% vs. 75.6%, p=0.098) and were less likely to being on maintenance oral corticosteroids (22% vs. 39.7%, p<0.0001). In this DTA cohort, positive HDM sensitisation was greater amongst the EMG than the White patients. The EMG status was a significant risk factor for HDM sensitisation.

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: ORBE II study

BackgroundThe ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain.MethodsORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables.ResultsA total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1–Q3) follow-up duration was 19.5 (14.2–24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes.ConclusionsThese data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP.Trial registrationNCT04648839.

Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids.

Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown. To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change. Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses. For the included 389 patients (55% female; mean body mass index, 28 ± 5 kg/m2; 58% maintenance OCS), mean weight decreased-0.27 kg/y (95% CI,-0.51 to-0.03; P= .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI,-1.21 to-0.52; P < .001] vs+0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (β=-0.24 kg/g; 95% CI,-0.38 to-0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (β= 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001). Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired.

Long-Term Real-World Outcomes of Mepolizumab and Benralizumab Among Biologic-Naive Patients With Severe Eosinophilic Asthma: Experience of 3 Years' Therapy.

Biologic therapies such as mepolizumab and benralizumab offer treatment options for severe eosinophilic asthma (SEA), although long-term real-world data on their use are limited. To evaluate the impact of benralizumab and mepolizumab treatment among biologic-naive patients with SEA over 36 months and describe the incidence of super-response at 12 and 36 months, identifying potential predictive factors. We conducted a retrospective, single-center study of patients with SEA who were given mepolizumab or benralizumab from May 2017 to December 2019, and who completed 36 months of therapy. Baseline demographics, comorbidities, and medication use were described. Data on clinical outcomes, including maintenance oral corticosteroid (OCS) use, annual exacerbation rate (AER), mini Asthma Quality of Life Questionnaire, Asthma Control Questionnaire (ACQ-6), and eosinophil count were collected at baseline and at 12 and 36 months. Super-response was evaluated at 12 and 36 months. A total of 81 patients were included. Maintenance OCS use significantly improved from baseline (5.3 mg/d) to 12months (2.4 mg/d, P < .0001) and 36 months (0.6 mg/d; P < .0001). Annual exacerbation rate decreased from baseline (5.8) to 12 months (0.9; P < .0001) and 36 months (1.2; P < .0001). Mini Asthma Quality of Life Questionnaire, ACQ-6, and eosinophil count significantly improved from baseline to 12 and 36 months. Twenty-nine patients demonstrated super-response at 12 months. Compared with those without a super-response, these patients had better baseline AER (4.7 vs 6.5; P= .009), mini Asthma Quality of Life Questionnaire (3.41 vs 2.54; P= .002), and ACQ-6 (3.38 vs 4.06; P= .03) scores. Most maintained a super-response up to 36 months. Mepolizumab and benralizumab are associated with significant improvements in OCS use, AER, and asthma control in real-world cohorts for up to 36 months, providing insight into long-term use for SEA.

Comprehensive Characterization of Difficult-to-Treat Asthma Reveals Near Absence of T2-Low Status.

Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a real-world understanding of this T2 paradigm in difficult-to-treat and severe asthma remains limited. To identify the prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiologic characteristics between patients classified as T2-high and T2-low. We evaluated 388 biologic-naive patients from the Wessex Asthma Cohort of difficult asthma (WATCH) study in the United Kingdom. Type 2-high asthma was defined as 20 parts per billion or greater FeNO , 150 cells/μL or greater peripheral blood eosinophils, the need for maintenance oral corticosteroids, and/or clinically allergy-driven asthma. This multicomponent assessment identified T2-high asthma in 93% of patients (360 of 388). Body mass index, inhaled corticosteroid dose, asthma exacerbations, and common comorbidities did not differ by T2 status. Significantly worse airflow limitation was found in T2-high compared with T2-low patients (FEV1/FVC 65.9% vs 74.6%). Moreover, 75% of patients defined as having T2-low asthma had raised peripheral blood eosinophils within the preceding 10 years, which left only seven patients (1.8%) who had never had T2 signals. Incorporation of sputum eosinophilia 2% or greater into the multicomponent definition in a subset of 117 patients with induced sputum data similarly found that 96% (112 of 117) met criteria for T2-high asthma, 50% of whom (56 of 112) had sputum eosinophils 2% or greater. Almost all patients with difficult-to-treat asthma have T2-high disease; less than 2% of patients never display T2-defining criteria. This highlights a need to assess T2 status comprehensively in clinical practice before labeling a patient with difficult-to-treat asthma as T2-low.

Mepolizumab in Patients With Severe Asthma and Comorbidities: 1-Year REALITI-A Analysis

Severe asthma is complex; comorbidities may influence disease outcomes. To assess mepolizumab effectiveness in patients with severe asthma and comorbidities. REALITI-A was a 2-year international, prospective study enrolling adults with asthma newly prescribed mepolizumab (100 mg subcutaneously) at physician's discretion. This post hoc analysis assessed 1-year outcomes stratified by comorbidities at enrollment: chronic rhinosinusitis with nasal polyps (CRSwNP), gastroesophageal reflux disease (GERD), depression/anxiety, and chronic obstructive pulmonary disease (COPD). Outcomes included the rate of clinically significant asthma exacerbations (CSEs; requiring systemic corticosteroids and/or hospital/emergency room admission) between the 12 months pre- and post-mepolizumab treatment and changes from baseline in daily maintenance oral corticosteroid dose (mo 12), Asthma Control Questionnaire-5 score (mo 12) and forced expiratory volume in 1 second (FEV1; mo 9-12). At enrollment (n= 822), 321 of 822 (39%), 309 of 801 (39%), 203 of 785 (26%), and 81 of 808 (10%) patients had comorbid CRSwNP, GERD, depression/anxiety, and COPD, respectively. Post- versus pre-treatment across all comorbidity subgroups: the rate of CSEs decreased by 63% or more; among 298 (39%) patients on maintenance oral corticosteroids at baseline, median dose decreased by 50% or more; Asthma Control Questionnaire-5 score decreased by 0.63 or more points; FEV1 increased by 74 mL or more. Patients with versus without CRSwNP had the greatest improvements (eg, rate of CSEs decreased by 75%). Patients without GERD, depression/anxiety, or COPD had greater improvements than those with the respective comorbidities, except for FEV1 in patients with COPD. Mepolizumab improved disease outcomes in patients with severe asthma irrespective of comorbidities, with additional benefit for patients with CRSwNP.

Potential impact of mepolizumab in stepping down anti-osteporotic treatment in corticosteroid-dependent asthma.

Oral corticosteroids (OCS) are commonly used for the acute management of severe asthma exacerbations or as maintenance therapy; however, chronic use is associated with significant toxicities, e.g., osteoporosis. In the REal worlD Effectiveness and Safety (REDES) study of mepolizumab in a multicentric Spanish cohort of asthma patients, mepolizumab effectively reduced clinically severe asthma exacerbations and decreased OCS dependence. This post-hoc analysis further evaluates mepolizumab's de-escalation effect on OCS dose. Patients enrolled in REDES who had OCS consumption data available for 12months pre- and post-mepolizumab treatment were included in this analysis. Primary outcomes were to determine the change in the proportion of patients eligible for anti-osteoporotic treatment due to the changes in OCS consumption before and after 1year of mepolizumab treatment. All analyses are descriptive. Approximately one-third (98/318; 30.8%) of patients in REDES were on maintenance OCS at the time of mepolizumab treatment initiation. In REDES, mean cumulative OCS exposure decreased by 54.3% after 1year of treatment. The proportion of patients on high-dose OCS (≥7.5mg/day) fell from 57.1% at baseline to 28.9% after 12months of mepolizumab treatment. Thus, 53.6% of OCS-dependent asthma patients treated with mepolizumab would cease to be candidates for anti-osteoporotic treatment according to guidelines thresholds.

Trait profiles in difficult-to-treat asthma: clinical impact and response to systematic assessment.

Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Among 241 patients; two airway-centric profiles were characterised by early-onset with allergic rhinitis (n=46) and adult-onset with eosinophilia/chronic rhino-sinusitis (n=60)), respectively, with minimal comorbid or psychosocial traits; three non-airway centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n=51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n=72), or multi-domain impairment (n=12). Compared to airway-centric profiles, non-airway centric profiles had worse baseline ACQ-6 (2.7 vs 2.2, p<0.001) and AQLQ (3.8 vs 4.5, p<0.001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs 2.2% predicted, p<0.05) while non-airway centric profiles trended to greater exacerbation reduction (1.7 vs 1.0, p=0.07); mOCS dose reduction was similar (3.1mg vs 3.5mg, p=0.782). Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.

Influence of chronic obstructive pulmonary disease on long-term hospitalization and mortality in patients with heart failure with reduced ejection fraction

BackgroundHeart failure with reduced ejection fraction (HFrEF) can coexist with chronic obstructive pulmonary disease (COPD), which complicates the clinical situation and worsens quality of life. The study used standard diagnostic criteria for detecting COPD in hospitalized HFrEF patients and to survey the influence of other comorbidities and medications on the long-term outcomes of HFrEF + COPD patients.MethodsWe retrospectively recruited patients hospitalized due to HFrEF in a tertiary medical center and examined and followed up clinical outcomes, including length of hospital stay, mortality, and readmission episodes, for a 5-year period. Risk factors for mortality were analyzed using multivariate analysis.ResultsOf the 118 hospitalized HFrEF study participants, 68 had concurrent COPD whereas 50 did not. There was a significant increase in the male predominance, smoking history, higher hemoglobin level and increased length of hospital stay in the HF + COPD group than in the HF-only group. Lower left ventricular ejection fraction was found in the HF and COPD comorbidity group. In multivariate analysis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use independently associated with a beneficial effect on survival in HF patients with COPD. Oral corticosteroid uses and stroke as a comorbidity were independently associated with a shorter time to the first readmission episode.ConclusionIn HFrEF patients, COPD was associated with a prolonged length of hospital stay. ACEI/ARB use might relate to a beneficial effect on survival in HF patients with COPD. The use of maintenance oral corticosteroid in patients with both HF and COPD should be crucially evaluated to determine the clinical benefit and disadvantages.

Real World Benefits of Mepolizumab in Patients With Severe Asthma and Comorbid Chronic Rhinosinusitis With Nasal Polyps (CRSwNP): Post Hoc Analysis of REALITI-A

In clinical trials, mepolizumab reduced clinically significant exacerbations (CSEs) and maintenance oral corticosteroid (mOCS) use in patients with severe eosinophilic asthma (SEA); greater benefits were observed in patients with comorbid CRSwNP. Equivalent long-term real-world data would enhance this evidence.

Real-World Impact of Mepolizumab on the Oral Corticosteroid Freedom Component of Clinical Remission in Severe Eosinophilic Asthma: International, Prospective REALITI-A Study

Reducing/eliminating oral corticosteroids (OCS) burden is a main aim of severe asthma management; OCS freedom is a key criterion of clinical remission. Mepolizumab reduces clinically significant asthma exacerbations (CSEs) and maintenance OCS (mOCS) use in patients with severe eosinophilic asthma.

Clinical response to benralizumab can be predicted by combining clinical outcomes at 3 months with baseline characteristics.

Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response. We assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (≥50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose. Benralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiver-operating characteristic (AUROC) 0.85 versus 0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3-65%), 67% (57-77%) and 97% (91-99%), respectively. In addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics.

Real-World clinical outcomes of asthma patients switched from reslizumab to mepolizumab or benralizumab.

Approximately 3%-10% of asthma patients will remain uncontrolled despite maximum, optimal conventional therapy. Treatment of severe refractory asthma often involves the use of targeted biological therapy. Randomised controlled trials have shown improvements in clinical parameters with these treatments but real-world data is lacking. The clinical parameters, frequency of exacerbations, number of hospital admissions, asthma control questionnaire score (ACQ), forced expiratory volume in one second (FEV1) and maintenance oral corticosteroid (OCS) dose of twenty asthma patients switched from reslizumab to benralizumab or mepolizumab at 1 year prior and 6 months after switching were compared, with adjustments for time. The mean frequency of exacerbations (0.35 v 0.3) and the mean ACQ were essentially unchanged (1.6 v 1.5) following the switch. The number of hospital admissions was one in the 6 months post switch compared to one in 1-year pre switch. 25% of patients were on maintenance OCS before and after switching but one patient required an increased dose post switch resulting in an increase in the mean maintenance OCS dose (1.6 mg to 2.4 mg). The mean FEV1 was unchanged (80% v 77.9%) six months post switching. Regarding asthma control (n = 19), 47.4% were controlled pre and post switch (ACQ < 1.5), 36.8% remained uncontrolled despite switching, 10.5% improved control while 5.3% disimproved. We present real-world clinical outcomes of asthma patients switched from reslizumab to either benralizumab or mepolizumab without a loss of clinical effectiveness in the majority.

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.

Severe asthma with fungal sensitization is associated with worse small airway dysfunction but similar symptom control

Severe asthma with fungal sensitization is associated with worse small airway dysfunction but similar symptom control

Efficacy and safety of dupilumab as add-on therapy for patients with severe asthma: A real-world Dutch cohort study

BackgroundDupilumab as add-on treatment for severe uncontrolled asthma (SA) has shown to be effective and safe by phase-III-trials. Real-world data on clinical efficacy and safety is limited. ObjectiveWe aim to investigate the efficacy and safety of dupilumab as add-on therapy for SA in a real-world cohort. Material and methodsThe primary endpoint was annually exacerbation-rate (AER). Secondary outcomes were maintenance oral corticosteroid (mOCS) dependency, asthma control (ACQ-5), pulmonary function (FEV1), quality of life (AQLQ) and frequency of reported adverse events (AEs). ResultsOverall, 148 patients were included. Median AER [IQR] reduced from 4.00 [2.00–5.00] at baseline to 1.00 [0.00–2.00] at 12 months (p < 0.001). mOCS-dependency reduced from 39.9% of the patients at baseline, to 20.3% at 6 months and to 14.9% at 12 months (p < 0.001). Median ACQ improved from 3.00 [2.00–3.80] at baseline to 1.80 [0.60–2.95] after 6 months and to 1.40 [0.20–2.60] after 12 months (p < 0.001). Median FEV1 (L) improved from 2.21 [1.58–2.85] to 2.50 [2.00–3.06] at 6 months and to 2.51 [1.88–3.04] after 12 months (p < 0.001). The outcomes improved most in subgroups with high eosinophils (≥300/μL) or FeNO (≥50 ppb) at baseline. AEs were reported by 45.3% (67/148), of which headache was most frequent. ConclusionsThis study indicates that dupilumab as add-on therapy for SA is associated with significant improvements in exacerbation-rate, mOCS-dependency, asthma control, pulmonary function, and quality of life. These results are in line with those of previous phase-III-trials.

Long-Term Efficacy and Clinical Remission After Benralizumab Treatment in Patients with Severe Eosinophilic Asthma: A Retrospective Study.

Few studies on the long-term efficacy of benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, have been conducted for patients with severe eosinophilic asthma (SEA), especially regarding the improvement of pulmonary function and clinical remission in a real-world setting. To elucidate the long-term efficacy and clinical remission rate (CRR) in patients with SEA. From July 2018 to July 2022, 23 Japanese patients with SEA received benralizumab for two years or more at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, biomarkers, number of exacerbations, pulmonary function, asthma symptoms, maintenance oral corticosteroid (OCS) dose and CRR. The mean observation period was 38.3 (24-49) months. Among the 23 patients, 10 patients switched from mepolizumab to benralizumab. After administration of benralizumab, the forced expiratory volume in one second (FEV1) increased and was maintained for two years in the biologic-naïve group and in the switching group (177 ± 404 and 151 ± 236 [mL], respectively, P = 0.80). In all patients, the %FEV1 improved from 76.7 ± 22.9% to 84.3 ± 18.4% (P = 0.016), and the number of annual exacerbations decreased from 2.5 ± 3.3 to 0.74 ± 1.7 (P = 0.014). Furthermore, the Asthma Control Test score significantly improved, and the reduction in OCS dose was maintained for three years. Ultimately, five patients met the clinical remission criteria and exhibited stabilization of pulmonary function, no exacerbation, no OCS use and well-controlled symptoms. The CRR was significantly higher in patients with a blood basophil count (BBC) ≥ 22 than in those with a BBC < 22 (/µL) (38.5% vs 0%, respectively, P = 0.046). Long-term treatment with benralizumab significantly improved pulmonary function, alleviated asthma symptoms and decreased the number of exacerbations at two years in a real-world setting. The CRR may be associated with the BBC at baseline.

ASTHMA EXACERBATIONS BEFORE AND AFTER TEZEPELUMAB TREATMENT: A POOLED ANALYSIS OF PATHWAY AND NAVIGATOR STUDIES

<h3>Introduction</h3> Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the PATHWAY and NAVIGATOR studies, tezepelumab reduced asthma exacerbations versus placebo in patients with severe, uncontrolled asthma, irrespective of baseline blood eosinophil count (BEC), allergic status and maintenance oral corticosteroid (mOCS) use. This post hoc pooled analysis assessed the effect of tezepelumab on asthma exacerbations 12 months before and after treatment initiation. <h3>Methods</h3> PATHWAY (NCT02054130) and NAVIGATOR (NCT03347279) were multicenter, randomized, placebo-controlled studies with similar designs. Patients (12–80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for up to 52 weeks were included. The mean number and rate of asthma exacerbations (accounting for time-at-risk) were summarized over 12 months before and after treatment initiation, respectively, for the overall pooled population and subgroups of baseline BEC, perennial allergic status and mOCS use. <h3>Results</h3> Overall, 1334 patients were included (tezepelumab, n=665; placebo, n=669). In the 12 months before treatment, the mean number of asthma exacerbations was similar between treatment groups in the overal population and across subgroups, except for those receiving mOCS (<b>Figure</b>). After up to 12 months of treatment, the rate of asthma exacerbations was lower with tezepelumab than the mean number of exacerbations before treatment and lower than the rate in the placebo group, overall and across subgroups (<b>Figure</b>). <h3>Conclusion</h3> Patients experienced fewer exacerbations after initiating tezepelumab treatment compared with the 12 months before treatment and compared with the placebo group. Similar reductions were observed irrespective of BEC, allergic status or mOCS use.

THE SUSTAINED OCS-SPARING EFFECT OF MEPOLIZUMAB: RESULTS FROM THE REAL-WORLD REALITI-A STUDY AT 2 YEARS

<h3>Introduction</h3> A main goal of asthma treatment is to reduce or eliminate oral corticosteroid (OCS) use due to their adverse effects. Clinical and real-world studies have reported mepolizumab reduces OCS use in patients with severe eosinophilic asthma (SEA); further evidence of the longer-term OCS-sparing effect of mepolizumab is needed. <h3>Methods</h3> REALITI-A was a 2-year international, prospective study, enrolling patients with asthma, newly prescribed mepolizumab 100 mg subcutaneously at physician's discretion. OCS-related outcomes were assessed at Weeks 53–56 and Weeks 101–104 in patients with baseline (28 days preceding mepolizumab initiation) maintenance OCS (mOCS) use and included: change from baseline in median mOCS dose, including stratification by mOCS dose categories, and proportion discontinuing mOCS. <h3>Results</h3> Of 822 patients treated, 320 (39%) had baseline mOCS use. Median (IQR) mOCS dose reduced from 10.0 (5.0, 14.7) mg/day at baseline (n=297) to 2.5 (0.0, 5.0) mg/day at Weeks 53–56 (n=218) and further to 0.0 (0.0, 5.0) mg/day at Weeks 101–104 (n=168), a 100% reduction. At baseline, 33% of patients (97/297) had a mean mOCS dose range of >10 mg/day, reducing to 10% (21/218) by Weeks 53–56 and 7% (12/168) by Weeks 101–104. In patients with baseline mOCS use, 43% (94/218) of patients discontinued mOCS use by Weeks 53–56, increasing to 57% (95/168) at Weeks 101–104. <h3>Conclusions</h3> During this 2-year real world study, mepolizumab demonstrated sustained and progressive OCS-sparing benefit in SEA, enabling a reduction in the burden associated with mOCS use for these patients.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study

BackgroundOral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored.Study populationA city-wide,...