Reduction In Exacerbations Research Articles

Eculizumab in refractory myasthenia gravis: a real-world single-center experience.

Immunosuppressive treatment is effective in most Myasthenia gravis patients, but 10-15% of patients areconsidered refractory due to inadequate response or intolerance to therapy. Eculizumab, a humanized monoclonalantibody directed against C5 complement protein, was approved in Italy to treat Ab-AchR generalized refractoryMG (rMG) in October 2022. We aim to describe a real-world Italian experience in a population of refractory myasthenia gravis patients with oneyear follow up. A retrospective data analysis was conducted on patients with refractory generalized MG treated with eculizumabbetween November 2022 and May 2024. Clinical assessment through specific scales (MG ADL - QMG - MGFA -PIS), rescue, and background therapy was recorded after one, three, six, and twelve months. 21 rMG patients were treated with eculizumab with a medium follow up of 10.4 months and 14 patients had at leastone year follow up. A clinically meaningful reduction in total MG-ADL and QMG scores was achieved in the firstmonth. It was maintained throughout the first, third, sixth, and twelfth month along with concomitant reduction ofimmunosuppressive treatments. A drastic reduction of myasthenic exacerbations and crisis was observed duringfollow up and intravenous immunoglobulin treatment was discontinued in all patients except one. The total dailydose of prednisone was significantly reduced. This single-center real-world study confirmes safety and effectiveness of eculizumab. Eculizumab improved rapidlyall clinical outcome measures, leading to discontinuation of intravenous immunoglobulin treatment and remarkable immunosuppressant-sparing benefits.

Implementation and effectiveness of guideline-recommended clinical activities for children with asthma: population-based cohort

BackgroundGuidelines advise minimising asthma exacerbation risk is achieved partially through good clinical practice activities, including scheduled asthma reviews, inhaler technique checks and asthma management plans. We assessed how frequently these activities are provided and how effective they are in clinical practice. Research questionDo guidelines-recommended activities such as asthma reviews, inhaler technique checks and asthma management plans prevent asthma exacerbations Study design and methodsThis is a retrospective chart review using UK primary-care medical records between 2004-2021, linked to hospital records. Children were eligible from asthma diagnosis until aged 16 years. Annual implementation of asthma review, inhaler technique check, management plan was measured. Risk factors for them not being undertaken were determined using multivariable logistic regression. Self-controlled case series (SCCS) was adopted to assess the effectiveness of each activity over 12-months; this was divided into two 6-month periods. Results126,483 children were eligible; 30-45% received each annual activity, 8% received all three together. Risk factors for not receiving activities included younger age, more socioeconomic deprivation, higher or no BMI measurement. Management plans and asthma reviews, as standalone activities, were associated with approximately 15% exacerbation reduction over 12-months and 8% over 6-months, respectively (management plan, N=4,624; 0-6 months (IRR, 95%CI): 0.87, 0.79-0.96; 6-12 months: 0.83, 0.73-0.95; asthma review, N=6,948; 0-6 months: 0.92, 0.85-0.99; 6-12 months: 0.93, 0.83-1.03). Standalone inhaler technique checks were not associated with exacerbations. Provision of all activities together was associated with approximately 30% exacerbation reduction over 12-months (N=3,643, 0-6 months: 0.76, 0.68-0.85; 6-12 months: 0.69, 0.60-0.81). InterpretationMost UK children do not receive the guideline-recommended activities to monitor their asthma. This study suggests, if implemented, they are effective in clinical practice and maximally effective when combined in the same visit.

Short-term Tezepelumab effectiveness in patients with severe asthma: a multicenter study

Objective Severe asthma presents significant management challenges, often requiring advanced treatments to control symptoms and reduce exacerbations. The use of monoclonal antibodies has revolutionized the clinical course of patients with severe asthma, showing a significant impact on exacerbations reduction, oral corticosteroids (OCS) cessation and on the improvement of lung function and quality of life. Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has emerged as a potential therapeutic option for these patients. Methods We conducted an observational, prospective, multicenter study including 20 patients with confirmed severe asthma according to ERS guidelines and GINA recommendations. Patients received Tezepelumab 210 mg every 4 wk due to uncontrolled asthma despite maximal inhalation treatment with ICS/LABA. Data were collected before treatment initiation (T0) and after three months from the first administration (T3). Results After three months of Tezepelumab treatment, we reported significant improvements in asthma symptoms and quality of life, as well as a consistent reduction in exacerbations and OCS use. We found no statistically meaningful differences among main clinical and functional outcomes according to inflammatory biomarkers, while lung function improved significantly in patients with less allergic sensitization. No serious adverse event was reported during the follow up, while the rates of mild adverse effects were comparable to those from registration trials. Conclusion Tezepelumab demonstrated short-term efficacy in improving asthma control and quality of life, showing a favorable safety profile. Further studies with larger sample sizes and longer follow-up would confirm these findings and identify predictors of response to Tezepelumab.

Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies.

In asthma, clinical response is characterized by disease improvement with treatment, whereas clinical remission is characterized by long-term disease stabilization with or without ongoing treatment. The proportion of patients receiving tezepelumab who responded to treatment and those who achieved on-treatment clinical remission was assessed in the NAVIGATOR (NCT03347279) and DESTINATION (NCT03706079) studies of severe, uncontrolled asthma. NAVIGATOR and DESTINATION were phase 3, randomized, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physicians' assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed. Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR: 2.83 [95% CI: 2.10-3.82]), and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR: 1.44 [95% CI: 0.95-2.19]) and weeks >52-104 (33.5% versus 26.7%; OR: 1.44 [95% CI: 0.97-2.14]). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarkers at baseline, and fewer exacerbations in the 12 months before the study. Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes but may be driven by different patient characteristics.

Effectiveness of anti-IL5/5Rα biologics in severe asthma in real world studies: a systematic review and meta-analysis

BackgroundThree biologics targeting interleukin 5 (anti-IL5) or its receptor-α (anti-IL5Ra) are approved for patients with severe asthma.MethodsWe conducted a systematic search until May 1, 2023, to identify observational studies and non-randomised trials that assess the response to anti-IL5/5Rα of real-life patients with severe eosinophilic asthma in MEDLINE and EMBASE. We performed random-effects meta-analyses.ResultsWe identified 6,401 studies of which 92 with 9546 patients were analysed. Biologics use was associated with 62% reduction in severe exacerbations (risk ratio, RR, 0.38, 95%CI 0.29 to 0.50) and 54% reduction in hospitalisations (RR 0.46, 95%CI 0.35 to 0.61) at 12 months of treatment, compared to pre-treatment. Biologics improved asthma control [decrease in asthma control questionnaire (ACQ) by 1.11 points (95%CI −1.29 to −0.94) and increase in asthma control test (ACT) by 6.41 points (95%CI 5.66 to 7.16)], and increased the asthma quality of life questionnaire (AQLQ) by 1.08 points (95%CI 0.88 to 1.28) and forced expiratory volume in 1 s (FEV1) by 0.21 L (95% CI 0.15 to 0.27) at 12 months. There was a significant reduction in oral corticosteroids use by 51% (RR 0.49, 95%CI 0.42 to 0.56), with a mean dose reduction of 6.01 mg/d (95%CI −7.55 to −4.48) at 12 months of treatment. Similar findings were observed at 3–4, 6 and 24 months. Biomarker-related response to treatment was also noted.ConclusionsThis comprehensive meta-analysis summarises the significant clinical response to anti-IL5/5Rα biologics in real-life studies, providing important insights for clinical practice use of these agents.

Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.

Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants. PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV1) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively. A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV1 % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators. Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.

Prospective REALITI-A Study: 2-Year Real-World Benefits of Mepolizumab in Severe Asthma

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is of proven clinical benefit in severe asthma; prospective, long-term, real-world data in severe asthma are required. Research QuestionThis study aimed to assess the real-world benefit of 2 years’ mepolizumab treatment in severe asthma. Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma, newly initiating mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year pre-mepolizumab versus 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSE; deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalisation), exacerbations requiring ED visit/hospitalisation, exacerbations requiring hospitalisation, proportion of patients with no exacerbations, median daily maintenance oral corticosteroid (mOCS) dose, proportion of patients discontinuing mOCS completely, asthma control questionnaire (ACQ)-5 score, forced expiratory volume in 1s (FEV1) and adverse events (AEs). ResultsAfter 2 years’ follow-up, 73% of patients (n=599/822) had no record of mepolizumab discontinuation. During the 2-year follow-up versus pre-mepolizumab period (N=822), rates of CSEs, exacerbations requiring ED visit/hospitalisation, or hospitalisation only were reduced by 74%, 79% and 73%, respectively (odds ratio for no CSEs: 10.0; 95% confidence interval: 7.55, 13.25). Median (Q1, Q3) daily mOCS dose decreased from 10.0 (5.0, 14.7) mg at Week 0 (n=297) to 0.0 (0.0, 5.0) mg at Weeks 101–104 (n=168), and the proportion of patients discontinuing mOCS increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in ACQ-5 scores from baseline at 2 years. At Months 21–24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (<1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively. InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well-tolerated, and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

Assessing the environmental justice implications of decarbonizing the US electric grid: estimating changes in asthma exacerbation by race and income

Abstract This paper examines how air quality improvements due to the 100% decarbonization of the US power sector in 2040 can reduce asthma exacerbation among children disaggregated by poverty status, race, and geography. Using spatial datasets that differentiate asthma prevalence by income, race, and state, we find that children living in households with income below the poverty line receive a disproportionate share of the benefits. To obtain these results, we employ several different federally administered datasets: American Community Survey, Behavioral Risk Factor Surveillance System (BRFSS), and Poverty Thresholds as provided by the US Census. We find that Black children and poor children, on average, have higher reductions in exposure to PM2.5. Nationally, close to 235 372 asthma exacerbation cases will be averted in 2040 under the decarbonization policy compared with Business-as-Usual. States with significant gains in asthma cases averted per 100 000 are Indiana, Kentucky, Ohio, Missouri, Pennsylvania, Texas, and Wisconsin. Furthermore, since the asthma portion of the BRFSS is not conducted in South Carolina, Colorado, Arkansas, and South Dakota, these states were omitted from the analysis. Across all states with significant gains, children living below the poverty line have larger health benefits than children above the poverty line. Households with child poverty have 50% larger reductions in asthma exacerbations than households without childhood poverty. Black children below the poverty line experience 33% higher health gains compared to Black children per 100 000 above the poverty line, 50% higher health gains compared to White children below the poverty line, and 159% higher than White children above the poverty line. We also provide general methodological insights for quantifying the environmental justice impacts of regulatory policies. We demonstrate why using race and poverty status-based prevalence rates is critical for understanding the distribution of health improvements and evaluating whether policies contribute to environmental justice goals.

Comparative effectiveness of dupilumab and omalizumab on asthma exacerbations and systemic corticosteroid prescriptions: Real-world US ADVANTAGE study

In the United States, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, and omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. This study assessed the real-world effectiveness of dupilumab and omalizumab for asthma in patients in the United States. In this retrospective observational study, TriNetX Dataworks electronic medical record data were used to identify patients with asthma age ≥12 years who initiated (index) dupilumab or omalizumab between November 2018 and September 2020 and who had at least 12 months of pre- and post-index clinical information. Inverse probability of treatment weighting was applied to balance potential confounding in treatment groups. Asthma exacerbation rates and systemic corticosteroid (SCS) prescriptions were compared using a doubly robust negative binomial regression model, adjusting for baseline exacerbation/SCS rates and patient characteristics with ≥10% standardized differences after inverse probability of treatment weighting. All inclusion and exclusion criteria were met by 2138 dupilumab patients and 1313 omalizumab patients. After weighting, the majority of baseline characteristics were balanced (standard difference <10%) between the 2 groups. Dupilumab was associated with a 44% lower asthma exacerbation rate (P< .0001) versus omalizumab. Additionally, dupilumab treatment significantly (P< .05) reduced SCS prescriptions by 28% during the follow-up period compared with omalizumab treatment. The US ADVANTAGE real-world study demonstrated a significant reduction in severe asthma exacerbations and SCS prescriptions for patients prescribed dupilumab compared with patients prescribed omalizumab during 12 months of follow-up.

Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

WPŁYW ADENOTONSILLEKTOMII NA KONTROLĘ ASTMY U PACJENTÓW PEDIATRYCZNYCH – PRZEGLĄD SYSTEMATYCZNY

IntroductionThis systematic review investigates the influence of adenotonsillectomy (AT) on asthma control in pediatric patients.Material and methodsA literature review from 2000 to 2023 based on the databases PubMed, the Cochrane Library, and Web of Science. The analysis is distilled down to four studies that revealed positive outcomes in asthma control as gauged by the Asthma Control Test (ACT), the Childhood Asthma Control Test (C-ACT), clinical outcomes, and asthma-related chitinase levels.ResultsThe four studies consistently demonstrated improved asthma control postoperatively in terms of improved ACT scores, reductions in acute asthma exacerbations, emergency room visits, hospitalisations, and medication usage. Notably, the correlation between improved asthma control and decreased chitinase activity suggests that AT has an impact on molecular markers associated with asthma.ConclusionsThe findings underline the potential benefits of AT in pediatric asthma management. However, the limitations of this study include a small number of studies and potential biases related to asthma’s natural course and seasonal variations. While the review provides evidence for the positive impact of AT on asthma control, further research with longer follow-up periods, case-matched controls, and consideration of seasonal factors is recommended.

Patient and clinician preferences for biologic treatments for severe uncontrolled asthma: a discrete choice experiment (DCE)

Objectives To estimate the preferences of patients with asthma and asthma-treating clinicians for attributes of biologic treatments, to compare patients’ and clinicians’ preferences, and to better understand the reasons for their preferences. Methods Adults with moderate-to-severe asthma and clinicians who treat asthma in the US completed a cross-sectional, online survey including a discrete choice experiment (DCE) that consisted of seven attributes spanning treatment efficacy, risk and convenience. Marginal utilities were estimated using a mixed logit model, and relative attribute importance scores calculated. Clinicians were also asked about the value of biomarker agnostic biologic treatments. The survey was followed by qualitative interviews targeting a sub-sample of survey participants, in which the rationale behind their survey responses was discussed. Results In the DCE, both patients and clinicians placed the most importance on exacerbation and hospitalization rate reduction, and risk of injection site reaction. Patients valued location of administration more than clinicians. Rationale for individual-level preferences varied, with patients and clinicians reporting their preference depended on event frequency and anticipated quality of life impacts. Clinicians mentioned compliance and financial impacts, while patients mentioned personal experience, particularly around site reactions. Most patients and clinicians would value a biomarker agnostic asthma treatment. Conclusions Asthma treatment preferences are largely driven by treatment efficacy and minimizing the risk of site reactions, although preferences differ between patients and clinicians across other attributes, highlighting the need for shared decision-making and individualized care.

Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear. The TriNetX Analytics Research Network, consisting of 120 million global de-identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n=6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n=37,906) and those on other FDA-approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n=2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF-related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS. ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5-2.75; p-value<0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54-5.85; p-value<0.0001). No significant differences occurred in secondary outcomes between ETI and non-CFTR modulator groups, except for reduced CF-related pulmonary exacerbations from 0 to 6 months post-FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators. In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study.

Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR. NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210mg or placebo subcutaneously every 4weeks for 52weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study. Tezepelumab reduced the AAER over 52weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline. These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers' treatment decisions. NAVIGATOR (NCT03347279).

Real-world effectiveness of dupilumab versus benralizumab and mepolizumab.

Introduction: In the United States, this real-world study compared the effectiveness of dupilumab, benralizumab, and mepolizumab in reducing exacerbations and systemic corticosteroid (SCS) prescriptions among patients with asthma. Methods: Patients (≥12 years old) who initiated dupilumab, benralizumab, or mepolizumab (index) between November 2018 and September 2020 were identified by using electronic medical record data. Subjects were included if they had ≥ 12 months of data before and after the index date and two or more severe asthma-related exacerbations before the index date. Differences in baseline characteristics were addressed by using inverse probability treatment weighting (IPTW). Pairwise comparisons between dupilumab and benralizumab, or mepolizumab were conducted by using negative binomial regression, adjusting for baseline rates and unbalance characteristics (≥10% standardized differences) after IPTW. Results: Overall, a total of 1737 subjects met all criteria: 825 dupilumab, 461 benralizumab, and 451 mepolizumab initiators. In the postindex period, dupilumab was associated with a 24% and 28% significant reduction in the risk of severe asthma exacerbations versus benralizumab (incidence rate ratio [IRR] 0.76 [95% confidence interval {CI}, 0.67-0.86)] and mepolizumab (IRR 0.72 [95% CI, 0.63-0.82]), respectively. In addition, dupilumab treatment significantly reduced SCS prescriptions by 16% and 25% versus benralizumab and mepolizumab, respectively (p < 0.05). Conclusion: This study represents one of the largest real-world comparisons of biologics (dupilumab, benralizumab, and mepolizumab) for asthma in the United States to date. This analysis shows that the use of dupilumab was associated with a significantly greater reduction in both severe asthma exacerbations and SCS prescriptions compared with benralizumab and mepolizumab.

APPaRENT 3: Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma in Seven Countries.

Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management. This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens. Overall, 1400 patients (mean age, 34years) and 599 physicians (mean age, 43years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score<20) and high symptom burden (39% reported nighttime awakenings or early mornings≥2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) with as-needed inhaled short-acting β2-agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever. Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA.

How to implement the anti-inflammatory reliever treatment proposed by the Global Initiative for Asthma in low- and middle-income countries

There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma

BackgroundSevere asthma pathology encompasses a wide range of pulmonary and extra-pulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health related quality of life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. ObjectiveTo examine the impact of pulmonary and extra-pulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centres. MethodsPatients characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. ResultsPatients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extra-pulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms and requirement for maintenance oral corticosteroids (OCS) was observed. ConclusionBoth pulmonary and extra-pulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasising the importance of early identification and management of severe asthma before comorbidities develop.

Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins

Chronic obstructive pulmonary disease (COPD) is a main global epidemic increasing as population age and affecting approximately 10% of subjects over 45 years. COPD is a heterogeneous inflammatory disease with several endo-phenotypes and clinical presentations. Although neutrophilic inflammation is canonically considered a hallmark of COPD, eosinophilic inflammation can also be present in a subgroup of patients. Several other immune cells and cytokines play a key role in orchestrating and perpetuating the inflammatory pathways in COPD, making them attractive targets for treating this disorder. Recent studies have started to evaluate the possible role of type 2 (T2) inflammation and epithelial-derived alarmins (TSLP and IL-33) in COPD. Two phase III randomized clinical trials (RCTs) showed a modest reduction in exacerbations in COPD patients with eosinophilic phenotype treated with mepolizumab (anti-IL-5) or benralizumab (anti-IL-5Rα). A phase III RCT showed a 30% reduction in exacerbations in COPD patients with ≥ 300 eosinophils/μL treated with dupilumab (anti-IL-4Rα). These results suggest that blocking a single cytokine (e.g., IL-5) or its main target (i.e., IL-5Rα) is less promising than blocking a wider spectrum of cytokines (i.e., IL-4 and IL-13) in COPD. TSLP and IL-33 are upstream regulators of T2-high and T2-low immune responses in airway inflammation. Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD.

Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort

BackgroundThe evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.MethodsOne thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1–4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.ResultsOne thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.ConclusionThese findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.Trial registrationTrial registration ClinicalTrials.gov, Identifier: NCT01245933.Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010–11, primary completion 2013–12, study completion 2023–09.https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3