Emerging treatments

Your Organizational Guidance

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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.[169] In phase 2 clinical trials, lebrikizumab reduced exacerbation rates and improved lung function in patients with uncontrolled asthma.[169][170] Efficacy was most pronounced in patients with high levels of blood eosinophils and periostin, both markers of type 2 inflammation.[169][170] Lebrikizumab subsequently failed to demonstrate consistent efficacy in biomarker-high patients in its pivotal phase 3 studies, and its development in asthma was discontinued in 2016.[171] 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.[172] One study of lebrikizumab in adolescent patients ages 12-17 years showed promising efficacy results but was prematurely terminated.[173] Meanwhile, the Food and Drug Administration has granted fast-track designation for lebrikizumab for the treatment of moderate-to-severe atopic dermatitis.

Itepekimab

Itepekimab is a human IgG4 monoclonal antibody directed against interleukin-33, an upstream epithelial alarmin involved in airway inflammation.[155][174] 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.[175] Itepekimab is also under clinical investigation in patients with chronic obstructive pulmonary disease.[176]

Vitamin D

Administration of vitamin D is associated with decreased rates of asthma exacerbations with very minimal adverse effects.[133][177] A randomized controlled trial (RCT) of adults with asthma and vitamin D deficiency showed that supplementation with weekly oral calcifediol compared with placebo improved asthma control test scores and quality of life over 6 months.[178] Despite these data, there is no clear consensus on how and when to supplement with vitamin D and which patients with asthma are most likely to benefit. It is currently not part of any of the major guidelines at this time but remains an active area for further investigation.[179][180] Guidelines indicate that correction of vitamin D deficiency in women with asthma who are pregnant, or planning pregnancy, may reduce the risk of wheezing episodes in their child's early life.[52] However, follow-up data from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) showed that prenatal supplementation failed to reduce incidence of asthma or recurrent wheeze in at-risk children at 6 years.[181] An RCT of vitamin D supplementation in children ages 6-16 years with persistent asthma and low vitamin D levels also failed to show improvement in severe exacerbations versus placebo.[182]

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