What are examples of immunomodulators used in ENT (Ears, Nose, and Throat)?

Immunomodulators Used in ENT (Ear, Nose, and Throat)

Corticosteroids are the primary and most effective immunomodulators used in ENT conditions, particularly intranasal corticosteroids for rhinosinusitis and allergic rhinitis. 1

Topical (Intranasal) Corticosteroids

Intranasal corticosteroids are the cornerstone of immunomodulatory therapy in ENT and are indicated for:

• Allergic rhinitis: First-line therapy for patients whose symptoms affect quality of life 1
• Chronic rhinosinusitis with nasal polyps (CRSwNP): Highly effective for reducing polyp size and improving symptoms 1
• Chronic rhinosinusitis without nasal polyps (CRSsNP): Improves disease-specific quality of life 1

Common intranasal corticosteroids include:

• Fluticasone propionate
• Mometasone furoate
• Budesonide
• Triamcinolone

Delivery Methods:

• Nasal sprays (most common)
• Nasal drops
• Nasal irrigation
• Exhalation delivery systems (newer technology showing improved delivery to sinuses) 1

Systemic Corticosteroids

Oral corticosteroids are used for:

• CRSwNP: Short courses (typically 1-3 weeks) provide significant but temporary improvement in polyp size and symptoms 1, 2
• Severe allergic rhinitis: Used in exceptional cases when intranasal steroids are insufficient 3

Common regimens include:

• Prednisolone 30-50mg daily for 5-14 days
• Methylprednisolone in tapering doses (e.g., 32mg/day days 1-5, 16mg/day days 6-10, 8mg/day days 11-20) 1

CAUTION: Oral corticosteroids should be limited to 1-2 courses per year due to potential adverse effects including mood disturbances, insomnia, and gastrointestinal issues 1, 2

Biologic Immunomodulators

Newer targeted immunomodulators are emerging for refractory ENT conditions:

• Anti-IgE (Omalizumab): For allergic rhinitis and nasal polyps with concurrent asthma 4
• Anti-IL-4Rα (Dupilumab): For CRSwNP 1, 5
• Anti-IL-5 agents: For eosinophilic CRSwNP 5

Other Immunomodulators

• Allergen immunotherapy: Effective for allergic rhinitis, potentially disease-modifying with sustained benefits after discontinuation 1

  • Subcutaneous immunotherapy (SCIT)
  • Sublingual immunotherapy (SLIT)

• Leukotriene receptor antagonists (LTRAs): Not recommended as primary therapy for allergic rhinitis 1

• Calcineurin inhibitors: Used in specialized cases of refractory ENT inflammation 5

Immunomodulators for Immune-Related Adverse Events

For immune checkpoint inhibitor-related ENT toxicities:

• TNF-α inhibitors (infliximab, adalimumab): For steroid-refractory inflammation 1, 5
• IL-6 receptor antagonists (tocilizumab): For specific cytokine-driven inflammation 1

Clinical Considerations

Efficacy

• Intranasal corticosteroids improve disease-specific quality of life with standardized mean difference of -5.46 (95% CI -8.08 to -2.84) compared to placebo 1
• Oral corticosteroids show large effect sizes for symptom improvement in the short term (2-3 weeks) but benefits are not sustained beyond 10 weeks 2

Safety Profile

• Second-generation intranasal steroids have minimal systemic bioavailability with excellent safety profiles 6, 3
• Monitor for local adverse effects such as epistaxis, nasal irritation, and rare cases of septal perforation 6
• Systemic corticosteroids carry higher risks including HPA axis suppression, mood changes, and metabolic effects 6, 2

Pitfalls to Avoid

1. Using oral corticosteroids as first-line therapy for uncomplicated allergic rhinitis
2. Prolonged or frequent courses of systemic corticosteroids
3. Failure to consider immunotherapy for allergic patients with inadequate response to pharmacotherapy
4. Overlooking the need for nasal saline irrigation as an adjunct to immunomodulatory therapy

Treatment Algorithm

1. For allergic rhinitis:

   • Start with intranasal corticosteroids
   • Add oral antihistamines for prominent itching/sneezing
   • Consider immunotherapy for inadequate response to pharmacotherapy
   • Reserve oral corticosteroids for severe, acute exacerbations only

2. For CRSwNP:

   • Begin with intranasal corticosteroids
   • Add short course of oral corticosteroids for significant symptoms/polyps
   • Consider biologic therapy for refractory cases
   • Surgical intervention for cases failing medical management

3. For CRSsNP:

   • Intranasal corticosteroids as primary immunomodulatory therapy
   • Limited role for oral corticosteroids
   • Consider antibiotics for acute bacterial exacerbations

4. For immune checkpoint inhibitor-related ENT toxicities:

   • Corticosteroids as first-line therapy
   • TNF-α inhibitors for steroid-refractory cases
   • Personalized anti-cytokine strategies based on specific manifestations

Remember that while immunomodulators effectively control symptoms, they generally do not cure the underlying condition, and therapy often needs to be continued long-term, particularly for chronic conditions like allergic rhinitis and CRSwNP.