Overview
Definition:
Biologic therapies for asthma are targeted treatments that modulate specific components of the inflammatory cascade
Anti-immunoglobulin E (anti-IgE) therapy, exemplified by omalizumab, targets IgE, a key mediator in allergic asthma
Anti-interleukin-5 (anti-IL-5) therapies, including mepolizumab, reslizumab, and benralizumab, target IL-5 or its receptor, which is crucial for eosinophil proliferation, maturation, and activation, particularly in eosinophilic asthma phenotypes.
Epidemiology:
Severe asthma affects approximately 5-10% of all asthma patients, with a significant proportion being children
In pediatrics, allergic asthma is common, often driven by IgE
Eosinophilic asthma, characterized by elevated blood eosinophil counts, is a distinct phenotype that responds well to anti-IL-5 therapies.
Clinical Significance:
These biologics offer a crucial therapeutic option for children with severe, uncontrolled asthma despite optimal standard care
They can reduce exacerbation rates, improve lung function, decrease oral corticosteroid dependence, and enhance quality of life
Understanding their mechanisms, indications, and adverse effects is vital for pediatricians and trainees preparing for DNB and NEET SS examinations.
Anti Ige Therapy
Mechanism Of Action:
Omalizumab is a recombinant humanized monoclonal antibody that binds to the Fc region of free IgE, preventing it from binding to mast cells and basophils
This reduces the release of inflammatory mediators upon allergen exposure.
Indications:
Approved for children aged 6 years and older with moderate to severe persistent allergic asthma that is inadequately controlled by inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA)
Requires evidence of sensitization to perennial aeroallergens and elevated IgE levels
Also indicated for chronic spontaneous urticaria in specific age groups.
Dosing Administration:
Dosage is based on body weight and serum IgE levels, typically administered every 2 or 4 weeks via subcutaneous injection
Dosing nomogram guides precise administration
For asthma, doses range from 75 mg to 375 mg every 2-4 weeks.
Adverse Effects:
Common side effects include injection site reactions (pain, redness, itching), headache, and pharyngitis
Rare but serious adverse events include anaphylaxis (risk during initial doses), and a potential increased risk of parasitic infections, especially in endemic areas
It is crucial to monitor for anaphylaxis closely during administration and for a period afterward.
Anti Il 5 Therapy
Mechanism Of Action:
Mepolizumab and reslizumab are monoclonal antibodies targeting IL-5, a cytokine essential for eosinophil development and function
Benralizumab is a monoclonal antibody that binds to the IL-5 receptor alpha subunit on eosinophils, leading to their depletion via antibody-dependent cell-mediated cytotoxicity
Targeting IL-5 or its receptor reduces eosinophil counts in the blood and airways.
Indications:
Indicated for children aged 12 years and older (reslizumab) or 6 years and older (mepolizumab, benralizumab) with severe eosinophilic asthma that is not controlled by high-dose ICS and LABA
Requires demonstration of elevated blood eosinophil counts (e.g., >150 cells/µL at baseline or >300 cells/µL in the past year) and evidence of at least one exacerbation in the past year.
Dosing Administration:
Mepolizumab: 100 mg subcutaneous injection every 4 weeks, or 300 mg intravenous infusion every 4 weeks for severe asthma
Reslizumab: 3 mg/kg intravenous infusion every 4 weeks
Benralizumab: 30 mg subcutaneous injection every 4 weeks for the first 3 doses, then every 8 weeks thereafter.
Adverse Effects:
Common side effects include nasopharyngitis, headache, and injection site reactions
Hypersensitivity reactions are possible
A key consideration is the potential for paradoxical bronchospasm and the risk of eosinophilic granulomatosis with polyangiitis (EGPA) in patients with pre-existing EGPA or other eosinophilic conditions when oral corticosteroids are reduced
Patients on chronic oral corticosteroids should have their dosage reduced gradually under medical supervision.
Selection And Monitoring
Patient Selection:
Careful phenotyping is essential
Anti-IgE is primarily for allergic asthma with elevated IgE and sensitization
Anti-IL-5 agents are for eosinophilic asthma phenotypes, identified by blood eosinophil counts and often a history of steroid dependence or frequent exacerbations
Shared decision-making with parents and the child is crucial.
Monitoring Efficacy:
Efficacy is assessed by reduction in asthma exacerbations, improvement in asthma control scores (e.g., ACT, c-ACT), lung function (FEV1), and reduction in oral corticosteroid use
Blood eosinophil counts should be monitored, especially when titrating ICS or oral steroids.
Monitoring Safety:
Regular follow-up is essential to monitor for adverse events, including hypersensitivity reactions, anaphylaxis (for omalizumab), and changes in symptoms suggestive of EGPA (for anti-IL-5 agents)
Periodic assessment of adherence and technique is also important.
Key Points
Exam Focus:
Understand the distinct mechanisms of anti-IgE and anti-IL-5 therapies
Recognize the specific phenotypes (allergic vs
eosinophilic asthma) and their corresponding biologic treatments
Memorize the age indications, dosing frequencies, and key adverse events for each biologic
Differentiate between IL-5 inhibitors and IL-5 receptor blockers.
Clinical Pearls:
Always confirm IgE levels and allergen sensitization before initiating omalizumab
For anti-IL-5 therapies, establish baseline eosinophil counts and monitor them during treatment
Titrate oral corticosteroids cautiously when initiating biologics
Educate patients and caregivers about the potential for anaphylaxis with omalizumab and EGPA with anti-IL-5 agents.
Common Mistakes:
Incorrectly selecting a biologic for the wrong asthma phenotype
Failing to adequately monitor for serious adverse events like anaphylaxis or EGPA
Not educating patients on proper injection technique or symptom recognition
Inadequate follow-up to assess treatment response and safety.