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Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

ABSTRACT: Background:Asthma affects millions of patients across the globe and also accounts for numerous mortalities every year. The current pharmacologic approach to the treatment of asthma includes the use of glucocorticoids and beta-agonists mainly. However, these conventional therapies have poor controllability of moderate-to-severe asthma and also produce several side effects on their long-term use. These limitations had led to the development of biologics targeting the mediators involved in T helper 2-inflammation associated with the pathogenesis of asthma such as interleukin (IL) 4, IL-5, and IL-13. dupilumab, a fully human monoclonal antibody, an IL-4 receptor alpha-antagonist targeting IL-13 and IL-4 has a potential role in treatment of moderate-to-severe asthma and was approved by the Food and Drug Administration on October 19, 2018. The dual-antagonistic action of dupilumab on IL-4 and IL-13 receptors renders it more efficient in asthma treatment. Objectives:To review the efficacy and safety profile of dupilumab in the treatment of moderate-to-severe asthma. Methods:Systematic search was performed via PubMed, Cochrane library, Embase, and ClinicalTrials.gov using the key words dupilumab, moderate-to-severe asthma, interleukin, IL-13, IL-4, and monoclonal antibody. Randomized controlled trials that compared between placebo and dupilumab in patients with uncontrolled asthma were included and observational studies were excluded in this review. Results:The review of selected literature reveals that addition of dupilumab to conventional therapy improves forced expiratory volume in 1 second and reduces the risk of severe asthma exacerbations in patients. No significant differences in incidence of adverse drug reactions/adverse drug events were observed between dupilumab and placebo groups except higher rates of injection site reactions in the dupilumab group. Conclusions:Concomitant use of dupilumab with long-acting beta agonists used in combination with inhaled corticosteroids, improves clinical outcomes and quality of life in patients with moderate to severe asthma. Although dupilumab has a promising role in treatment of patients with asthma, it is still in the emerging stage for its acceptance globally. Ongoing studies will help to determine dupilumab's long-term efficacy and safety for its future extensive use.

SUBMITTER: Rathinam KK

PROVIDER: S-EPMC6911908 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

Rathinam Kiran Kumar KK Abraham Justin Jacob JJ Vijayakumar Thangavel Mahalingam TM

Current therapeutic research, clinical and experimental 20191028

<h4>Background</h4>Asthma affects millions of patients across the globe and also accounts for numerous mortalities every year. The current pharmacologic approach to the treatment of asthma includes the use of glucocorticoids and beta-agonists mainly. However, these conventional therapies have poor controllability of moderate-to-severe asthma and also produce several side effects on their long-term use. These limitations had led to the development of biologics targeting the mediators involved in ...[more]

PMID: 31871508

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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:BackgroundBullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.MethodsMedical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).ResultsThe median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22-90 years) and 64.50 years (range: 17-86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1-240 months) and 2.5 months (range: 1-60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1-13 days) and 12 days (range: 5-21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624-2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708-4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100-10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900-14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded.ConclusionsDupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.

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Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

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Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

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