New perspectives of childhood asthma treatment with biologics

Abstract

Asthma is no longer considered as a single disease but rather as a syndrome corresponding to different entities and pathophysiologic pathways. A targeted strategy is part of personalized medicine which aims to better define each patient's phenotype and endotype so as to prescribe the most suitable treatment at an individual level. Omalizumab and, more recently, mepolizumab are the first biologics approved for children (6‐18 years). Omalizumab is now widely used to treat severe allergic asthma in children and is highly effective for asthma exacerbations and asthma control with a good safety profile. Moreover, several other drugs—lebrikizumab, dupilumab, tezepelumab, mepolizumab, reslizumab, benralizumab—are used or are being studied in both teenagers and adults and could benefit younger children in the near future. We hypothesize that defining the asthma phenotype/endotype regarding the type and intensity of inflammation, association with allergic or non‐allergic comorbidities, and airway remodeling should contribute to the choice of a specific biologic. Pediatric specificities have to be addressed and validated by studies in children. Long‐term effectiveness and particularly the impact on the natural history of asthma should also be investigated. Severe asthma in children is a complex disease, and patients have to be referred to a specialized pediatric asthma center to confirm diagnosis and initiate the best treatment strategy which could include biologics while taking into account their high cost.

Omalizumab and mepolizumab in the landscape of biological therapy for severe asthma in children: how to choose?

“…Biological drugs can be an option in case of severe asthma [70][71][72]. Among the biological drugs currently available, today omalizumab is the one with the biggest amount of data on efficacy and safety, and the one we have more real-life clinical experience with [73].…”

The environment and its effect on allergic sensitization and atopic dermatitis, and colostrum and the immune system of the preterm infant

“…For decades, no new medications had been developed, and the introduction of biologics, now also more and more with an indication in pediatric patients, has revolutionized the treatment of asthma. In the second review, Just et al provide most welcome guidance for the use of current and new treatment options.…”

Estado actual del uso de medicamentos biológicos en asma grave

“…El fenotipo hace referencia a las características clínicas observables de la enfermedad, mientras que el endotipo se relaciona con el mecanismo biológico subyacente, con biomarcadores específicos. El tratamiento dirigido por biomarcadores es parte de la medicina de precisión cuyo objetivo final es la adaptación de estrategias preventivas y terapéuticas a las características de cada paciente a fin de obtener el mejor resultado clínico individual 5,6 . Se reconocen dos endotipos de asma: T2 elevado (asma esosinofílica) y T2 disminuido o No-T2 (asma no eosinofílica) 5,7,8 .…”

“…Tanto los mastocitos como los basófilos expresan en su membrana el receptor de alta afinidad para IgE (FcεR1) y son activados por el entrecruzamiento de 2 de dichos receptores mediante la unión de una mólecula de IgE específica a los mismos. Una vez activados, los mastocitos secretan histamina, PGD2, CysLTs y triptasa propagando la respuesta inflamatoria 6 . El principal biomarcador del endotipo T2 es un número elevado de eosinófilos en las vías aéreas.…”

“…Los fenotipos T2 aumentado incluyen: asma alérgica de inicio temprano, asma eosinofílica de inicio tardío en la edad adulta, y la enfermedad respiratoria exacerbada por aspirina (AERD). Algunos autores incluyen otros dos fenotipos: asma inducida por ejercicio y la aspergilosis broncopulmonar alérgica 5,6 . Los fenotipos correspondientes a la respuesta T2 disminuida son el asma relacionada con obesidad de inicio tardío, el asma paucigranulocítica y el asma neutrofílica.…”