What is the evidence for immunotherapy (allergy shots) in treating asthma?

Evidence for Immunotherapy in Asthma

Allergen immunotherapy (AIT) is an effective adjunctive treatment for patients with mild-to-moderate allergic asthma who have demonstrated IgE sensitization to unavoidable aeroallergens and inadequate symptom control despite appropriate pharmacotherapy. 1

Patient Selection Criteria

Consider AIT for asthmatic patients when ALL of the following are present:

• Clear relationship between asthma symptoms and exposure to unavoidable aeroallergens (house dust mite, pollens, animal dander) 1
• Documented specific IgE antibodies via skin testing or serum testing 1
• Inadequate control with pharmacotherapy and/or environmental avoidance measures 1
• Mild-to-moderate asthma severity (FEV1 >70-80% predicted) 1, 2
• Controlled asthma at baseline (not during acute exacerbation) 1, 3

Additional favorable characteristics include:

• Coexisting allergic rhinitis 1
• Long duration of symptoms (perennial or major portion of year) 1
• Patient desire to avoid long-term pharmacotherapy 1
• Unacceptable medication side effects 1

Clinical Efficacy Evidence

The 2024 American Academy of Otolaryngology guidelines cite high-quality evidence (61 RCTs and multiple systematic reviews) supporting AIT effectiveness in allergic asthma. 1

Symptom and medication outcomes:

• Significant reduction in asthma symptoms (standardized mean difference -0.59,95% CI -0.83 to -0.35) 4
• Number needed to treat = 3 patients to prevent one deterioration in symptoms 4
• Number needed to treat = 4 patients to avoid one requiring increased medication 4
• Reduction in inhaled corticosteroid use while maintaining asthma control in mild-to-moderate disease 1

Bronchial hyperreactivity:

• Significant reduction in allergen-specific bronchial hyperreactivity 4
• Some reduction in non-specific bronchial hyperreactivity 4
• Improved quality of life measures 1

Specific Allergen Evidence

House dust mite: The strongest evidence exists for subcutaneous immunotherapy (SCIT) with multiple double-blind, placebo-controlled studies demonstrating efficacy 1. Sublingual immunotherapy (SLIT) tablets show efficacy in reducing asthma exacerbations when used as add-on therapy in adults 5, 6

Pollens (grass, birch, ragweed): SCIT demonstrates clinical and significant effects on early asthmatic response in children and adults 1, 5

Animal dander: Evidence supports efficacy, though less extensive than for mites and pollens 1, 4

Molds and cockroach: Evidence is weak or lacking 1, 7

Disease-Modifying Effects

AIT represents the only treatment demonstrating continued symptom control after cessation of therapy. 1

Long-term benefits include:

• Sustained symptom improvement for years after discontinuation 1
• Prevention of new allergen sensitizations 1
• Potential prevention of asthma development in children with allergic rhinitis 1
• Possible increased remission rates in children 6

Absolute Contraindications

Do NOT initiate AIT in patients with:

• Uncontrolled asthma at time of treatment 1, 3
• Severe asthma (increases risk of life-threatening reactions) 3
• Pregnancy 1
• Inability to tolerate injectable epinephrine 1
• Age <5 years (particularly for SLIT due to cooperation and safety concerns) 3

Route of Administration: SCIT vs SLIT

Subcutaneous immunotherapy (SCIT):

• Recommended by NAEPP Focused Updates as adjunctive treatment for allergic asthma 1
• Stronger evidence base for asthma outcomes 2, 6
• Requires administration in medical setting with observation period 1

Sublingual immunotherapy (SLIT):

• NOT recommended for asthma treatment per NAEPP Expert Panel guidelines 3, 2
• May be used if allergic rhinitis is present as complication, with potential asthma benefits 6
• Considered investigational in United States for asthma (no FDA-approved formulation) 8
• Favorable safety profile but less robust asthma efficacy data 8, 2

Safety Profile and Adverse Events

Local reactions: Number needed to harm = 16 patients (one expected local reaction) 4

Systemic reactions: Number needed to harm = 9 patients (one expected systemic reaction of any severity) 4

Risk mitigation:

• Ensure asthma is controlled before each injection 1, 3
• Administer in setting equipped for anaphylaxis management 1
• Observe patients for 30 minutes post-injection 1
• Avoid administration during acute asthma exacerbations 3

Integration with Pharmacotherapy

AIT should be used as adjunctive therapy, not replacement for controller medications. 1

The stepwise approach:

• Continue inhaled corticosteroids as foundation of asthma management 1, 2
• Add AIT when symptoms remain inadequately controlled despite appropriate pharmacotherapy 1
• Consider biologic agents (omalizumab) to optimize asthma control before initiating AIT in borderline candidates 5
• For severe allergic asthma, optimize with biologics rather than AIT 3, 2

Optimal Candidates Based on Phenotype

Field studies suggest best responders are:

• Polysensitized patients with rhinitis and GINA class 2-4 asthma 5
• Those demonstrating high eosinophilic response to allergen exposure 5
• Children and adults with documented allergen-specific bronchial hyperreactivity 5

Common Pitfalls to Avoid

Do not initiate AIT without:

• Confirming IgE sensitization correlates with clinical symptoms and exposure history 1
• Ensuring asthma is controlled at baseline (not just stable) 1, 3
• Verifying patient can access emergency care and tolerate epinephrine 1

Do not use AIT as monotherapy - it must be combined with appropriate controller medications 1

Do not continue AIT if no clinical benefit after first year of treatment (approximately 35% of patients show no response) 8