Asthma in adults

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

Astma bij volwassenen: diagnose en monitoring in de eerste lijnPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2020Asthme chez l’adulte : diagnostic et surveillance en soins de santé primairesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2020

Lebrikizumab

Lebrikizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that binds to interleukin-13 and inhibits its function.[255] Despite showing promise in phase 2 studies, lebrikizumab subsequently failed to demonstrate consistent efficacy in biomarker-high patients in pivotal phase 3 studies, and its development in asthma was discontinued in 2016.[255][256][257] However, in 2021, authors of a post-hoc analysis of the phase 3 data found that patients enrolled in the trials may have been underdosed, opening up the possibility of new trials at higher doses.[257][258] Another post-hoc analysis of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation enrolled using the same phase 3 data suggested that lebrikizumab significantly reduced asthma exacerbations.[257][259] One study of lebrikizumab in adolescent patients ages 12-17 years showed promising efficacy results but was prematurely terminated.[260] Lebrikizumab is currently approved for the treatment of atopic dermatitis, but not for the treatment of asthma.

Itepekimab

Itepekimab is an investigational human IgG4 monoclonal antibody directed against interleukin-33, an upstream epithelial alarmin involved in airway inflammation that shows biological plausibility and promise in phase 1 studies.[229][261][262] In a phase 2 study of patients with moderate-to-severe asthma, itepekimab monotherapy was associated with fewer loss-of-control asthma events than dupilumab monotherapy, dupilumab plus itepekimab, or placebo.[263] Itepekimab is also under clinical investigation in patients with chronic obstructive pulmonary disease.[264]

Depemokimab

Depemokimab is an investigational, ultra-long-acting biologic therapy that binds to interleukin-5 and could allow 6-month dosing intervals. Two phase 3, randomized, placebo-controlled trials (SWIFT-1 and SWIFT-2) have evaluated the efficacy and safety of depemokimab in 760 adults and adolescents ages 12 years or older with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite medium- or high-dose inhaled corticosteroids.[265] Treatment with depemokimab using 6-month dosing intervals improved the annualized exacerbation rate at 52 weeks by 54% compared with placebo, without increasing in adverse events.

Masitinib

Masitinib is an investigational oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor signaling implicated in asthma pathogenesis. One randomized, double-blind, placebo-controlled, phase 3 trial, assessing the efficacy and safety of masitinib in severe uncontrolled asthma (despite the use of high-dose inhaled corticosteroids, long-acting beta-agonists, and oral corticosteroids) showed that masitinib reduces the risk of exacerbations in severe asthma and has an acceptable safety profile.[266]

Vitamin D

Vitamin D supplementation remains an active area of investigation. One meta-analysis suggested that vitamin D supplementation may reduce the rate of asthma exacerbations requiring systemic corticosteroids and a second suggested that it may improve lung function (i.e., FEV₁/FVC) and immune function (i.e., IL-5, IL-10, and IgE).[92][93][94] While a third meta-analysis showed that vitamin D supplementation increased anti-inflammatory (IL-10) levels, it reported no effect on biomarkers of type 2 inflammation (i.e., serum IgE, blood or sputum eosinophils, and FeNO).[94] However, one Cochrane review found no evidence to support a role for vitamin D supplementation in reducing exacerbation risk or improving asthma control.[91] It concluded that further research is required to clarify potential effects of calcidiol on the risk of asthma exacerbations and to determine whether vitamin D supplementation improves asthma in those with severe disease or the lowest baseline levels of vitamin D (<25 nmol/L).[91]

Statins

Statins may be associated with a lower risk of asthma exacerbations and better clinical outcomes in adult asthma.[267] Although use does not appear to change lung function, statins may exert beneficial effects by reducing inflammation, particularly through reductions in serum high-sensitivity C-reactive protein, sputum eosinophils, and interleukin-6 levels.[268][269][270][271] Further research is needed.[268]

Metformin

Metformin may represent a novel treatment for asthma associated with metabolic dysfunction.[272] A large UK cohort study of new metformin users with type 2 diabetes and asthma found that metformin was associated with a lower rate of asthma attacks in all asthma phenotypes, suggesting that this function was associated with mechanisms other than glycemic control or weight loss.[273] A systematic review and meta-analysis found a potential but nonsignificant reduction in the incidence of newly developed asthma, asthma exacerbations, asthma-related emergency department visits, and systemic corticosteroid prescribing in studies of patients with type 2 diabetes who used metformin.[274] Further clinical research is needed, but early evidence suggests that antidiabetic drugs may reduce the frequency of asthma attacks in patients with obesity who have diabetes.[272]

Glucagon-like peptide-1 (GLP-1) receptor agonists

GLP-1 receptor agonists may represent a novel treatment for asthma associated with metabolic dysfunction, possibly by targeting the GLP-1 receptor that is present in lung epithelial and endothelial cells.[275] One retrospective cohort study of patients with type 2 diabetes and asthma newly prescribed GLP-1 receptor agonists or comparator showed that the GLP-1 receptor agonist group had fewer asthma exacerbations.[276] Another cohort study reported that GLP-1 receptor agonists further reduced the rate of asthma attacks when added to metformin.[273] GLP-1 receptor agonists in preclinical murine and ex vivo models has also been shown to significantly inhibit allergic and viral airway inflammation, including the associated airway eosinophilia, mucus production, and hyperresponsiveness.[275][277][278][279] Further clinical research is needed, but early evidence suggests that antidiabetic drugs may reduce the frequency of asthma attacks in patients with obesity who have diabetes.[272]

Use of this content is subject to our disclaimer