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Dupilumab rapidly improves asthma control in predominantly anti-IL5/IL5R pretreated Austrian real-life severe asthmatics.

ABSTRACT: Dupilumab is a monoclonal antibody against the IL-4 receptor alpha which has shown efficacy in T2 high severe asthmatics in phase 3 randomized controlled trials. The purpose of this real-life study is to demonstrate the real-life effectiveness of dupilumab in Austrian severe asthma patients. We retrospectively analyzed all patients receiving dupilumab at our severe asthma clinic. Thirteen patients have so far received dupilumab at our center. The primary outcome, asthma control questionnaire 6-item scale at 2 weeks, improved by 0.57 points (p = .014), which is statistically and clinically significant. Similarly, the asthma control test at 4 weeks improved by 3.91 points (p = .024), also statistically and clinically significant. Improvements in forced expiratory volume in 1 s at 2 weeks were neither statistically, nor clinically significant. Improvements at 4 weeks (+220 ml, p = .041), and 3 months (+229 ml, p = .006), were statistically significant and clinically borderline significant. No severe adverse events or hypereosinophilia were observed. No adverse events led to treatment discontinuation. Most patients (85%) had previously received monoclonal antibody treatment for severe asthma. Previous monoclonal antibody treatment had been discontinued in these patients due to a lack of clinical response. Dupilumab is effective and safe in Austrian real-life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti-immunoglobulin E or anti-IL5/IL5R monoclonal antibody treatments or do not adequately respond to these.

SUBMITTER: Renner A

PROVIDER: S-EPMC8342226 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200?mg or 300?mg every 2?weeks reduced exacerbations and improved forced expiratory volume in 1?s (FEV1) and quality of life over 52?weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods:Patients were randomised to 52?weeks of subcutaneous dupilumab 200?mg every 2 weeks, 300?mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ?150?eosinophils·µL-1, ?300?eosinophils·µL-1, ?25?ppb fractional exhaled nitric oxide (F eNO), and both ?150?eosinophils·µL-1 and ?25?ppb F eNO, at baseline. Results:Dupilumab treatment (200?mg and 300?mg every 2?weeks) resulted in significant improvements versus placebo after 52?weeks in pre-bronchodilator FEV1 (0.20 and 0.13?L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13?L, respectively), forced vital capacity (FVC) (0.20 and 0.14?L, respectively), forced expiratory flow (0.19 and 0.13?L·s-1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4-52) was significant (0.04?L·year-1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F eNO levels for most outcomes. Conclusions:Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

Project description:BackgroundSevere asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates.ObjectiveThis systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data.MethodsClinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV1 ) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).ResultsA total of 21 studies examining biologicals in real-world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualzsed exacerbation rate significantly by -3.79 (95% confidence interval [CI] -4.53, -3.04), -3.17 (95% CI -3.74, -2.59) and -6.72 (95% CI -8.47, -4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV1 (0.17 L 95% CI 0.11, 0.24) and FeNO (-14.23 ppb 95% CI -19.71, -8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV1 (0.21 L 95% CI 0.08, 0.34).ConclusionsThese data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.

Project description:BackgroundEmpirical research and health policies on asthma have focused on children and young adults, even though asthma morbidity and mortality are higher among older asthmatics.ObjectiveTo explore the relationship of asthma-related beliefs and self-reported controller medication adherence in older asthmatics.DesignAn observational study of asthma beliefs and self-management among older adults.ParticipantsAsthmatics ages ? 60 years (N?=?324, mean age 67.4 ± 6.8, 28 % white, 32 % black, 30 % Hispanic) were recruited from primary care practices in New York City and Chicago.Main measuresSelf-reported controller medication adherence was assessed using the Medication Adherence Report Scale. Based on the Common Sense Model of Self-Regulation, patients were asked if they believe they only have asthma with symptoms, their physician can cure their asthma, and if their asthma will persist. Beliefs on the benefit, necessity and concerns of treatment use were also assessed. Multivariate logistic regression was used to examine the association of beliefs with self-reported medication adherence.Key resultsThe majority (57.0 %) of patients reported poor adherence. Poor self-reported adherence was more common among those with erroneous beliefs about asthma illness and treatments, including the "no symptoms, no asthma" belief (58.7 % vs. 31.7 %, respectively, p?<?0.001), "will not always have asthma" belief (34.8 % vs. 12.5 %, p?<?0.001), and the "MD can cure asthma" belief (21.7 % vs. 9.6 %, p?=?0.01). Adjusting for illness beliefs, treatment beliefs and demographics, patients with a "no symptoms, no asthma" belief had lower odds of having good self-reported adherence (odds ratio [OR] 0.45, 95 % confidence interval [CI] 0.23-0.86), as did those with negative beliefs about the benefits (OR 0.73, 95 % CI 0.57-0.94) and necessity (OR 0.89, 95 % CI 0.83-0.96) of treatment.ConclusionsIllness and treatment beliefs have a strong influence on self-reported medication adherence in older asthmatics. Interventions to improve medication adherence in older asthmatics by modifying illness and treatment beliefs warrant study.

Project description:BackgroundBullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients.ObjectiveWe evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth.Methods and resultsA multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment.ConclusionDupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.

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Dupilumab rapidly improves asthma control in predominantly anti-IL5/IL5R pretreated Austrian real-life severe asthmatics.

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