Current State and Future of Biologic Therapies in the Treatment of Asthma in Children

Abstract

There is increasing recognition of phenotypic variability in pediatric asthma, providing the opportunity for a more personalized approach to therapy. Increasingly biologic therapies, in particular those targeting the ''allergic'' (or T helper 2) pathway, are being considered for children with severe asthma. However, there is a great deal of variability in the extent these biologic therapies have been studied in children, as well as efficacy of results thus far. The goal of this article is to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of the biologic medications focusing on the pediatric population, in an effort to establish a more personalized approach to asthma in the pediatric population for the 21st century.

Efficacy of omalizumab in children, adolescents, and adults with severe allergic asthma: a systematic review, meta-analysis, and call for new trials using current guidelines for assessment of severe asthma

“…Although the omalizumab data available are increasing in the adult population, it is extremely limited in the adolescent population and even more limited in those < 12 years of age. In the era of new evolving biologicals to target specific inflammatory phenotypes of severe asthma [50] there is an imminent need for new trials with strict systematic assessments and better case definitions to determine the benefits of the drugs in the true severe asthma population, which are seen in the respiratory outpatient clinics. Of importance, since omalizumab was first approved by FDA in 2003 the definition of severe asthma has changed and now requires a systematic assessment to rule out difficultto-treat asthma and does not include a lung function criterion anymore.…”

“…Considering cost issues and what our needs are at present in the severe asthma field, where new biologicals are being developed continuously, it would be perhaps more costeffective to focus on head-to-head studies with other biological agents rather than having another study of a single biological agent vs placebo. Newer trials should preferably compare placebo to both omalizumab and new anti-IgE drugs in the pipeline (such as ligelizumab, which may be more potent than omalizumab [50]), as well as focus on head-to-head trials in "real world" settings. This also implies addressing the "real world" problems such as the fact that some patients on biologics taper down or even stop taking their controller medication such as ICS, which may lead to a poorer clinical response to the biological agent; addressing the fact that some patients need switching from one biological to another, where efficacy of such regime needs to be investigated in clinical trials; and ultimately comparing treatment efficacy of biologicals in patients with severe asthma vs. difficult-to-treat asthma as the latter may also benefit from biologicals and could be a target group if the cost of biological treatment drops in the future.…”

Severe asthma: Entering an era of new concepts and emerging therapies: Highlights of the 4th international severe asthma forum, Madrid, 2018

“…Rather than increasing pharmacotherapy in the non-responsive child, co-morbidities, social and environmental factors should be addressed, especially poor adherence. In addition to omalizumab, at least 3 additional biologicals (mepolizumab, benralizumab, dupilumab) should become available soon for childhood severe asthma (9). To enable personalised treatment approaches further research into response predictors is key.…”

Can early intervention in pediatric asthma improve long‐term outcomes? A question that needs an answer

“…However, specific data in children younger than 12 years and even adolescents are limited. Furthermore, the long‐term effects of these therapies remain to be seen; more investigation is still necessary to determine if biologic therapy can prevent disease progression or even reverse airway damage . One agent targeting IgE, which plays a role in allergen sensitization and airway inflammation, is omalizumab, an anti‐IgE monoclonal antibody approved by the US Food and Drug Administration (FDA) for asthma with atopy in patients aged ≥6 years .…”

“…Furthermore, the long-term effects of these therapies remain to be seen; more investigation is still necessary to determine if biologic therapy can prevent disease progression or even reverse airway damage. 57 One agent targeting IgE, which plays a role in allergen sensitization and airway inflammation, is omalizumab, an anti-IgE monoclonal antibody approved by the US Food and Drug Administration (FDA) for asthma with atopy in patients aged ≥6 years. 58 One study in children aged 6-12 years showed that omalizumab treatment resulted in a larger median reduction in maintenance ICS dosage (100%) compared with placebo (66.7%, P = 0.001), and also significantly reduced the percentage of patients with severe exacerbations (18.2%) compared with placebo (38.5%, P < 0.001) during the 12-week ICS dose-reduction phase of the study.…”