Oral Corticosteroid Use Research Articles

Unmet Need for Oral Corticosteroids Use and Exacerbations of Asthma in Primary Care in Taiwan.

Patients with asthma are treated in primary healthcare facilities (PHCFs) in Taiwan, where the asthma control status associated with acute exacerbation (AE) and use of oral corticosteroids (OCS) and short-acting β2-agonist (SABA) inhalers remains unclear. A cross-sectional, close-ended, face-to-face questionnaire survey invited board-certified physicians who treat adult asthma patients in PHCFs. The contents of the questionnaire included three parts: rescue OCS to treat AE, regular OCS for asthma control, and AE-related adverse outcomes. There were 445 out of 500 physicians who completed the questionnaire, with 61% of them being non-pulmonologists. A substantial proportion of asthma patients needed rescue OCS or regular OCS each month, or ≥3 canisters of SABA inhalers per year. Approximately 86% of physicians reported their patients with ≥2 AE-related unscheduled visits to clinics or emergency departments in the past year. A total of 41% of physicians reported their patients receiving intubation or intensive care in the past year. A total of 92% of physicians prescribed rescue OCS ≤ 40 mg/day. A total of 92% of physicians prescribed rescue OCS for a duration of ≤7 days for AEs. A total of 85% of physicians prescribed regular OCS ≤ 10 mg/day for asthma control. This is the first study to present the perceptions of asthma-treating physicians on the use of OCS in PHCFs. In summary, 31% of physicians reported ≥ 6% of their patients needed OCS for asthma control and 41% of physicians reported their patients with adverse outcomes in the past year. Thus, the need to improve asthma control in Taiwan is suggested by our study results.

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

The long-term effect of dupilumab on dyspnea, sleep, and activity in oral corticosteroid-dependent severe asthma

BackgroundSevere asthma impacts quality of life (QoL), including dyspnea, sleep, and activity limitation. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4 and -13, which are key and central drivers of type 2 inflammation. Phase 3 LIBERTY ASTHMA VENTURE (NCT02528214) and LIBERTY ASTHMA TRAVERSE open-label extension (NCT02134028) evaluated dupilumab 300 mg vs placebo every 2 weeks for 24 weeks (VENTURE) and dupilumab only for an additional 48 to 96 weeks (TRAVERSE) in patients with oral corticosteroid (OCS)-dependent severe asthma. ObjectiveTo assess dupilumab's impact on Asthma QoL Questionnaire (AQLQ) items related to breathing symptoms, sleep, and activity limitation, and on OCS reduction. MethodsThe proportion of patients with AQLQ scores of 6 or 7 for breathing symptoms-, sleeping-, and activity-related items in VENTURE and TRAVERSE, together with OCS dose reductions in VENTURE. ResultsIn VENTURE, significantly greater proportions of dupilumab- vs placebo-treated patients achieved scores of 6 or 7 by week 24 in breathing symptoms-related (42.7%-60.2% vs 22.4%-39.3%), sleeping-related (45.6%-65.0% vs 27.1%-47.7%), and activity-related (44.7%-51.5% vs 22.4%-34.6%) AQLQ items. Improvements were maintained through TRAVERSE in the dupilumab/dupilumab group and increased to dupilumab treatment levels in the placebo/dupilumab group. Significant OCS dose reductions were observed in VENTURE; up to 90% and 60% of dupilumab-treated vs 65% and 41% of placebo-treated patients with AQLQ scores of 6 or 7 in breathing symptoms-, sleeping-, and activity-related items achieved greater than or equal to 50% dose reduction and eliminated OCS at week 24, respectively. ConclusionIn patients with severe OCS-dependent asthma, dupilumab improved QoL related to breathing symptoms, sleep, and activity limitation, and reduced OCS use. Trial RegistrationClinicalTrials.gov Identifiers: NCT02528214 and NCT02134028.

Proactive Risk Management: A Novel Approach to Embedding Oral Corticosteroid Stewardship into Asthma Care

The continued inclusion of oral corticosteroids (OCS) in treatment guidelines, as well as the accessibility, familiarity, and relatively low cost of this therapeutic option compared with newer alternatives, has contributed to an ongoing overreliance on OCS treatments in severe asthma. This overuse continues despite accumulating evidence to demonstrate the detrimental long-term effects associated with even a short-term, low-dose course of OCS in this patient population. OCS Stewardship is a collaborative, systematic effort designed to protect patients with asthma from inappropriate OCS use through a series of patient- and physician-focused initiatives. Ultimately, OCS Stewardship aims to reduce OCS-related morbidity, lower the risk of OCS-related adverse events (AE), increase health-related quality of life, and reduce healthcare resource utilisation. This article summarises data that were exhibited as part of the European Respiratory Society (ERS) International Congress held in Barcelona, Spain, describing a novel proactive risk-management approach to embedding OCS Stewardship into asthma care. The objectives of this meeting were to highlight the latest data demonstrating the need for OCS Stewardship in asthma; discuss approaches to assessing OCS exposure and OCS-related toxicities, and the rationale for systematic assessment of OCS toxicity in individual patients; and to consider practical tools to evaluate future risk of asthma exacerbations and OCS-related adverse effects. Also described in this article are three posters, which were presented during the same meeting, and provide further data to support OCS-sparing activities in severe asthma by AstraZeneca.

Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma

BackgroundSevere neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised...

Prevalence, comorbidities, and treatment patterns of Japanese patients with alopecia areata: A descriptive study using Japan medical data center claims database.

Real-world data on alopecia areata (AA) demographics, comorbidities, and treatment patterns are sparse, not only in Japan but worldwide. This cross-sectional study assessed the current prevalence of AA in Japan, including analysis of severe subsets, frequency of comorbidities, and unmet medical needs surrounding treatment. Patients registered in the Japan Medical Data Center claims database (January 2012 to December 2019) and diagnosed with AA were included. Prevalence was calculated yearly, with the most common comorbidities evaluated, and treatments described in the Japanese Dermatological Association AA management guidelines and approved in Japan were included in the analysis. In total, 61 899 patients were diagnosed with AA. Among them, 1497 were diagnosed with severe subtypes. AA prevalence in Japan has been gradually increasing (from 0.16% in 2012 to 0.27% in 2019). The most common comorbidities are allergic rhinitis, atopic dermatitis, and asthma. Depression and anxiety are frequent in these patients, as are autoimmune diseases, e.g., vitiligo, thyroid diseases, and rheumatoid arthritis. Intriguingly, the analysis found Down syndrome to be a comorbidity associated with severe AA in children. The principal treatments were topical corticosteroids, followed by carpronium chloride and cepharanthine. The use of systemic corticosteroids and antihistamines is increased in severe disease. The Japanese Dermatological Association guidelines do not support the use of oral corticosteroids in children; however, in the database, this has been prescribed in up to 2.5% and 9.8% of all pediatric and severe pediatric AA cases, respectively. Despite the limitations of using a claims database, the current study demonstrates that AA prevalence in Japan has gradually increased in recent years, with allergic diseases being the most common comorbidities. The data also imply that there is a need for effective and safe therapies, especially for severe and pediatric cases.

REAL-WORLD BENRALIZUMAB EFFECTIVENESS AMONG ASTHMA PATIENTS WITH COMORBID NASAL POLYPS: RESULTS FROM THE ZEPHYR2 STUDY

<h3>Introduction</h3> Benralizumab demonstrated significant reductions in asthma exacerbations among asthma patients with comorbid nasal polyps (NP). This study characterized the real-world effectiveness of benralizumab pre- vs. post-initiation in a population stratified by prior NP surgery. <h3>Methods</h3> In this pre-post study, asthma patients with comorbid NP were identified from a large US insurance claims database (11/2016–6/2020). Patients were aged ≥12 years, with ≥2 records of benralizumab, ≥2 exacerbations pre-benralizumab use (index date), and an NP diagnosis in the 12-months pre-index. Patients were stratified by NP surgery in the 12-months pre-index. Asthma exacerbation rates and NP-related outpatient and oral corticosteroid (OCS) use were described and compared between the 12-month pre-index and post-index periods. <h3>Results</h3> Among the 241 patients identified, 66 had pre-index NP surgery and 175 did not. The surgery cohort had on average 2.5 pre-index NP surgeries vs. 0.3 post-index. The non-surgery cohort had 0 pre-index vs. 0.4 surgeries post-index. The overall NP cohort experienced a 58% reduction in exacerbation rates, with a 57% reduction seen in the surgery cohort and a 59% reduction in the non-surgery cohort (all p<0.001, see Figure). Percentages of patients with NP-related outpatient visits (surgery: 100% pre-index vs. 61% post-index; non-surgery: 96% vs. 62%; both p<0.001) and OCS use (surgery: 79% vs. 36%; non-surgery: 78% vs. 37%; both p<0.001) decreased in both cohorts. <h3>Conclusion</h3> In the pre-post analysis, patients with asthma and comorbid NP, irrespective of NP surgery profile, experienced significant reductions in asthma exacerbations, NP-related outpatient visits and OCS use following benralizumab.

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.

Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm3: A Post Hoc Analysis from the ANANKE Study.

Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300-450 cells/mm3 subset of patients. Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300-450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected. A total of 164 patients were analyzed, 34 of whom with a BEC of 300-450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300-450 subset showed similar reductions in AER (-94.8% vs -92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered. At baseline, apart from lower severe exacerbation rate, the BEC 300-450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300-450 patients as in the total population.

REAL-WORLD EFFECTIVENESS OF DUPILUMAB ON ORAL CORTICOSTEROID USE IN PATIENTS WITH MODERATE-TO-SEVERE ASTHMA

<h3>Introduction</h3> Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in asthma. Patients with oral-corticosteroid (OCS)-dependent severe asthma are at increased risk of OCS-related adverse events. In phase 3 VENTURE (NCT02528214), add-on dupilumab 300 mg every 2 weeks vs placebo reduced OCS maintenance dose in patients with OCS-dependent severe asthma. Dupilumab demonstrated an acceptable safety profile. We investigated the real-world effectiveness of dupilumab in reducing OCS use in patients with OCS-dependent severe asthma. <h3>Methods</h3> This retrospective, single-arm study analyzed data from the Avalere Claims database, a large US insurance claims database. Patients diagnosed with moderate-to-severe asthma (GINA 4/5) initiating dupilumab between November 1, 2018, and July 31, 2019, were included. Exclusion criteria were chronic obstructive pulmonary disease (COPD) diagnosis or treatment with another biologic for asthma in the previous year. There were 141 OCS-dependent patients included in this analysis (<b>Table</b>). The proportions of patients with any OCS use, mean annualized cumulative OCS dose, and percentage of patients with ≥90 days of OCS use were assessed pre and post 12 months of dupilumab initiation. <h3>Results</h3> Dupilumab significantly reduced the proportion of patients with any OCS use by 20.6% [<i>P</i>=<0.0001], the mean annualized cumulative OCS dose by 33.4% [<i>P</i>=<0.01], and patients with ≥90 days of OCS-use by 42% [<i>P</i>=<0.0001] in OCS-dependent patients from the 12-month pre baseline to the 12-month follow-up period. <h3>Conclusion</h3> Dupilumab is effective in reducing OCS use in patients with moderate-to-severe OCS-dependent asthma in real-world settings.

Characteristics of Oral Corticosteroid Users Among Persons with Asthma on GINA Step 3 Therapy and Above: A Cross-Sectional Study in Portuguese Community Pharmacies.

Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA). Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®). A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users). These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients.

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.

Effects of Inhaled Corticosteroids on Bone in Asthma Patients

Background: Although inhaled corticosteroids are taken into the bloodstream, it is unclear how much damage they do to bones. The issue is crucial because 3% of people consistently use inhaled corticosteroids and could be doing for several decades. Method: In 195 adults (118 women) with asthmatic, aged 25 to 45, we examined the dose-response relationship between total inhaled corticosteroid dosage and bone mineralization concentration at the lumbar region and proximal femur. Participants had received only a little amount of systemic steroids and had routinely used an inhaled corticosteroid for a minimum of six months. Multiple regression analysis was employed to evaluate the total dosage of inhaled corticosteroid's impact on the density of bones from surveys, computerized general practitioners' data, and printed and handwritten general medical documents. Results: Treatment with inhaled corticosteroids lasted an average of 6 years (0–23), with a baseline total dose of 875 mg (87–4370). Both before and after adjusting for the influences of aging and gender, the results showed a negative correlation between the total dose of inhaled corticosteroid and skeletal mineral density at the lumbar region (L2-L4), femoral neck, and trochanter. An increase in inhaled corticosteroid dosage by twofold was linked to a 0•17 SD (95% CI 0•03-0•27) reduction in lumbar spine concentration of bone minerals... The femoral neck and trochanter all showed identical declines. The relationships remained strong after controlling for possible influencing variables such as regular exercise and previous use of oral, intranasal, cutaneous, and injectable corticosteroids. Conclusion: This investigation shows a link between the overall average dosage of inhaled corticosteroids and decreased bone mineralization concentration in asthmatic sufferers. Keywords: Corticosteroids, fracture, bone mineralization, inhaled, dosage, asthma, lumbar region, femur

The Italian severe/uncontrolled asthma registry (RItA): A 12-month clinical follow-up

Backgroundfollow-up studies on registries of severe/uncontrolled asthma (SUA) patients are scanty. Objectiveto analyze baseline and follow-up characteristics of SUA patients and their longitudinal patterns. Methods180 adult patients (age ≥15 yrs) were investigated at baseline and 12-month follow-up through the Italian SUA registry (RItA).Latent transition analysis (LTA) was performed to detect cross-sectional SUA phenotypes and longitudinal patterns. Risk factors for longitudinal patterns were assessed through logistic regression. Resultsa significant/borderline improvement of asthma control outcomes in the last 2–4 weeks emerged at follow-up with respect to baseline for: daily activities limitations (Δ −16%), frequent diurnal symptoms (Δ −25%), uncontrolled asthma symptoms according to ACT (Δ −26%). Last 12-month use of oral corticosteroids was less frequent at follow-up than at baseline (Δ −25%). Health status improvement was confirmed by lung function test results.Through LTA, two longitudinal patterns were detected considering last 12-month control outcomes: “persistence/worsening” (53.9%), “under control/improvement” (46.1%). A lower likelihood of having “persistence/worsening” SUA was exhibited by patients under anti-IgE (OR 0.38, 95% CI 0.17–0.84) and inhaled corticosteroids-bronchodilator association treatment (OR 0.13, 95% CI 0.01–1.26, borderline value), while a higher likelihood was shown by older age at first asthma diagnosis (OR 1.04, 95% CI 1.01–1.07). Conclusionthe implementation of a SUA registry, the availability of patient-level data and the application of an innovative longitudinal analysis allowed to observe a general improvement in asthma control, one year after baseline, and a lower risk of SUA “persistence/worsening” in patients under anti-IgE and regular ICS-bronchodilator association use.

Impact of Mepolizumab on Exacerbations in the US Medicare Population

Asthma is a common chronic respiratory disorder associated with significant disease and economic burden. Mepolizumab is an anti-IL-5 mAb approved for use as an add-on treatment in patients with severe eosinophilic asthma. To assess the impact of mepolizumab initiation on asthma exacerbation frequency, oral corticosteroid (OCS) use, and asthma exacerbation-related costs in a US Medicare population. This was a retrospective cohort study of mepolizumab claims from patients with asthma in the Centers for Medicare and Medicaid Services Medicare database carried out between January 2016 and December 2018. The index date (first claim for mepolizumab) was required to occur between January and December 2017. The baseline and follow-up periods were the 12 months before and 12 months after the index, respectively. Outcomes included changes in the proportion of patients experiencing exacerbations (primary), OCS use (secondary), and asthma exacerbation-related costs during the baseline and follow-up periods. The study identified 1,278 patients (mean age, 67.9 years; 65% female) with one or more prescription or administration claim for mepolizumab who were eligible for study inclusion. There was a significant relative reduction in the proportion of patients with an asthma exacerbation (27%; P < .0001) in the follow-up versus baseline period. Similarly, a lower proportion of patients received OCS for asthma (16% relative reduction; P < .0001), fewer patients were chronic OCS users (5 mg/day or more; 48% relative reduction; P < .0001), and there was a significant decrease in asthma exacerbation-related costs (total reduction, $888; P= .0002) during the follow-up versus the baseline period. Mepolizumab reduced exacerbations, OCS use, and exacerbation-related healthcare costs in a US Medicare population, confirming its benefits in this specific population with severe asthma.

Use of FeNO to predict anti-IL-5 and IL-5R biologics efficacy in a real-world cohort of adults with severe eosinophilic asthma

Introduction Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. Methods We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. Results Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. Conclusion In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb.

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Is Omalizumab Related to Ear and Labyrinth Disorders? A Disproportionality Analysis Based on a Global Pharmacovigilance Database.

Introduction: Asthma is a chronic disease, characterized by reversible airway obstruction, hypersensitivity reactions, and inflammation. Oral corticosteroids are an important treatment option for patients with severe or steroid-resistant asthma. Biologics for asthma are recommended in patients with severe asthma, owing to their steroid-sparing effect as well as their ability to reduce the severity and aggravation of uncontrolled asthma. Most clinical trials of omalizumab in patients with asthma have suggested its tolerability and safety. However, some studies reported eosinophilic comorbidities in the ear, nose, and throat during omalizumab treatment, particularly eosinophilic otitis media. This study examined the relationship between ear disorders and omalizumab compared with that of other biologics for asthma using a large real-world database. Materials and Methods: Individual case safety reports from the Uppsala Monitoring Centre Vigibase of biologics for asthma (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) up to 29 December 2019, were used. A disproportionality analysis was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information components (IC). A hierarchy analysis used the Medical Dictionary for Regulatory Activities Terminology. A tree map was generated using R studio version 4.2. Results: In 32,618 omalizumab reports, 714 adverse events (AEs) were detected as signals. Among the 714 signals, seventeen AEs were detected as signals of omalizumab-related ear and labyrinth disorders in 394 reports. Only three AEs (ear pain, ear disorder, and ear discomfort) were detected from mepolizumab. No signal was detected from reslizumab, benralizumab, and dupilumab. Conclusions: Careful monitoring of ear disorders is recommended when omalizumab treatment is started, with decreased oral corticosteroid use in patients with severe asthma. Further studies are necessary to confirm the omalizumab-related signals.

A case series of dual biologics therapy for severe asthma

Treatment with monoclonal antibodies (mAb) targeting IgE, IL-5, and IL-4/IL-13 pathways has become the standard strategy to manage severe asthmatics refractory to conventional therapies. Biologics are effective in improving symptom control, exacerbation rates, and oral corticosteroid (OCS) dependence.1 However, a subset of patients show suboptimal response, manifesting as persistent OCS use and functional decline.2 Given the complex relationship between cytokines, immune cells, and structural cells in driving the pathophysiology of asthma, it is conceivable that targeting a single pathway may be insufficient for optimal asthma control.