3 biologic drugs available for pediatric patients with severe asthma
Katie A.Krone, M.D. and Emily M.DeBoer, M.D., FAAP
Focus on Subspecialties
Mariah is a 6-year-old, followed closely in your practice, with a history of atopy
and persistent asthma that is poorly controlled despite leukotriene blockade and high-dose
inhaled corticosteroid (ICS)/long-acting beta-agonist therapy. She requires frequent
courses of oral steroids.
You have established a veritable diagnosis of asthma, evaluated for alternative diagnoses
and comorbid conditions that contribute to a more severe asthma phenotype, and assessed
medication adherence and delivery technique. Now, you are wondering if there is a
role for biologic therapies.
As you facilitate referral to a pediatric allergist/pulmonologist for further evaluation
in anticipation of escalation of care (Step 5 outlined in the Global Initiative for
Asthma Management, https://ginasthma.org), Mariah’s family asks what other medications are available to manage her asthma.
Which of the following statements are true?
a. Targeted biologic therapies are available for treating allergic and eosinophilic
b. Omalizumab has been approved for children ages 6 years and older.
c. Biologic therapies should be assessed after four to six weeks to determine response
d. Mepolizumab is available as a subcutaneous injection for eosinophilic asthma in
children 12 years of age and older.
e. Benralizumab is available as an intravenous formulation for eosinophilic asthma
in children 12 years of age and older.
Answer: a, b and d are true
The Food and Drug Administration has approved three biologic drugs for use in pediatric
patients 18 years of age and younger with severe asthma: omalizumab (anti-IgE monoclonal
antibody), mepolizumab (anti-IL-5 monoclonal antibody) and benralizumab (anti-IL-5
Omalizumab was introduced in 2002 and in 2016 was approved to treat uncontrolled allergic
asthma in children as young as 6 years of age. Outcome data have demonstrated clinical
efficacy as well as safety in the pediatric population as evidenced by reduction in
asthma exacerbation frequency, symptom days and ICS dose.
Omalizumab is administered subcutaneously in a monitored setting and dosed every two
to four weeks based on age, pretreatment serum IgE levels (30-1,300 IU/mL) and body
weight. Anaphylaxis is rare (≤0.2%) (Chipps, BE, et al.J Allergy Clin Immunol. 2017;139:1431-1444).
Mepolizumab and benralizumab — anti-IL5 therapies for treatment of severe eosinophilic
asthma (blood eosinophils ≥300 cells/µL in past 12 months) — were approved in 2015
and 2017, respectively, for adolescents ages 12 years and older. Both are administered
subcutaneously. Published clinical trials have shown decreased exacerbation rates
and a reduction in daily maintenance oral steroid dose.
Reslizumab, available in IV formulation, was approved in 2016 for adults 18 years
of age and older.
Deciding which therapy to initiate requires an individualized approach, focusing on
history of atopy, biomarkers, prior treatment response, asthma control goals and potential
adverse effects. If a biologic drug does not provide benefit after a four- to six-month
trial, it is reasonable to allow for a six-week washout and then trial another biologic
(provided the patient meets criteria for an alternative biologic drug).
While severe asthma affects a small subset of children with asthma (about 10%), these
patients and their families are disproportionately burdened by health care visits,
missed work and school, morbidity and adverse quality of life. Further, children with
severe asthma are a heterogeneous subset, creating complexity in predicting responsiveness
to targeted therapies as well as achieving asthma control.
Management of severe asthma is a prime area for application of personalized medicine
and targeted therapies. Future advances may be made through the identification of
new biomarkers as well as the development of new biologic therapies, such as the anti-IL13
and anti-IL4 drugs in the pipeline (Katial RK, et al. J Allergy Clin Immunol Pract. 2017;5(2s):s1-s14).
Mariah is seen by an asthma specialist. Given her uncontrolled asthma, age, perennial
allergies and IgE of 300, she is started on omalizumab. At her follow-up visit with
you, her family expresses gratitude for your practical knowledge of the use, indications
and side effects of the biologics that facilitated the next steps in her care.
Asthma management strategies are detailed in the Global Initiative for Asthma Management.
National Heart, Lung, and Blood Institute asthma guidelines are undergoing revision.
Use of targeted asthma therapies with currently available and new biologic drugs is
likely to alter treatment paradigms.
Better elucidation of severe pediatric asthma endotypes will further inform the development
of targeted therapies and delivery of personalized medicine.
Dr. Krone is an AAP Fellowship Trainee member. She and Dr. DeBoer are members of the
AAP Section on Pediatric Pulmonology and Sleep Medicine Executive Committee.