What is the role of Tezspire (tezepelumab) in healing severe asthma?

Tezspire (Tezepelumab) in Severe Asthma Management

Tezspire is an FDA-approved add-on maintenance treatment for severe, uncontrolled asthma in patients aged 12 years and older who remain symptomatic despite high-dose inhaled corticosteroids plus long-acting beta-agonists, and it works by blocking thymic stromal lymphopoietin (TSLP) to reduce inflammation across multiple asthma phenotypes. 1, 2

Mechanism and Unique Position

Tezepelumab is a human monoclonal antibody that blocks TSLP, an epithelial cytokine that initiates and perpetuates airway inflammation in asthma. 2, 3 Unlike other biologic therapies that target downstream inflammatory mediators, tezepelumab acts at an earlier point in the inflammatory cascade, providing broader anti-inflammatory effects across different asthma phenotypes. 3

Clinical Efficacy Across Asthma Phenotypes

The most compelling evidence comes from the NAVIGATOR trial (2021), which demonstrated that tezepelumab reduced annualized asthma exacerbation rates by 56% compared to placebo (0.93 vs 2.10 exacerbations per year; rate ratio 0.44, P<0.001). 2

Key efficacy outcomes include:

• Eosinophilic severe asthma: 63-71% reduction in exacerbations 3
• Allergic severe asthma: 58-68% reduction in exacerbations 3
• Type 2-low asthma: 34-49% reduction in exacerbations (notably effective even in patients with blood eosinophils <300 cells/μL, with rate ratio 0.59, P<0.001) 2, 3
• Oral corticosteroid-dependent asthma: 31-41% reduction in exacerbations 3

Improvements in Lung Function and Quality of Life

At 52 weeks, tezepelumab demonstrated:

• Prebronchodilator FEV1 improvement of 0.13 liters versus placebo (0.23 vs 0.09 liters; P<0.001) 2
• Asthma Control Questionnaire-6 (ACQ-6) score improvement of -0.33 points (P<0.001) 2
• Asthma Quality of Life Questionnaire (AQLQ) improvement of 0.34 points (P<0.001) 2
• Meta-analysis confirmed FEV1 improvement of 0.15 L maintained at 24 and 52 weeks 4

Long-Term Safety Profile

The DESTINATION extension study (2023) evaluated safety over 104 weeks and found:

• Adverse event incidence of 49.62 per 100 patient-years with tezepelumab versus 62.66 with placebo (difference -13.04) 5
• Serious adverse event incidence of 7.85 per 100 patient-years versus 12.45 with placebo (difference -4.59) 5
• No higher incidence of adverse drug reactions compared to placebo (pooled proportion 0.79,95% CI: 0.55 to 1.12) 4
• Most common side effects: sore throat, joint pain, and back pain 1

Critical Safety Considerations and Contraindications

Tezepelumab is contraindicated in patients with known hypersensitivity to tezepelumab-ekko or any ingredients. 1

Mandatory Safety Precautions:

• Risk of hypersensitivity reactions including anaphylaxis: Can occur within hours or have delayed onset (days after administration) 1
• Not for acute asthma symptoms or exacerbations: Patients must seek medical advice if asthma remains uncontrolled or worsens 1
• Cannot abruptly reduce corticosteroids: Reduction must be under direct physician supervision to avoid systemic withdrawal symptoms 1
• Avoid live attenuated vaccines: Patients should inform providers about tezepelumab use before vaccination 1
• Parasitic infections: Should be treated before initiating tezepelumab 1

Populations Requiring Caution:

Based on general asthma biologic principles and guideline recommendations for similar therapies:

• Uncontrolled or severe asthma patients should have asthma optimized before initiating biologics, as poorly controlled asthma increases risk of severe reactions 6
• Pregnancy: Limited data available; discuss risks and benefits with healthcare provider 1
• Children under 12 years: Safety and efficacy not established 1

Administration Protocol

• Dosing: 210 mg subcutaneously every 4 weeks 1, 2
• Setting: Should be administered by healthcare providers trained to recognize and treat anaphylaxis 7, 8
• Storage: Refrigerate at 36°F to 46°F (2°C to 8°C); may be kept at room temperature (68°F to 77°F) for maximum 30 days 1
• Self-administration: Patients or caregivers may administer after proper training, but initial doses should be supervised 1

Position in Treatment Algorithm

According to current asthma management guidelines:

• Step 5-6 therapy: Tezepelumab is indicated when patients remain uncontrolled despite high-dose ICS-LABA therapy 6, 7, 8
• Before oral corticosteroids: Consider as add-on therapy before initiating or to reduce oral corticosteroid burden 6
• Broad applicability: Unlike other biologics (omalizumab for allergic asthma, anti-IL5 for eosinophilic asthma), tezepelumab demonstrates efficacy across phenotypes including Type 2-low asthma 2, 3

Common Pitfalls to Avoid

• Do not use as monotherapy: Must be used as add-on to existing controller medications 8
• Do not use for acute symptoms: This is maintenance therapy only, not rescue treatment 1
• Do not discontinue corticosteroids abruptly: Taper only under medical supervision 1
• Do not assume immediate effect: While some patients respond rapidly, full benefits may take several weeks 2
• Do not overlook adherence and technique: Optimize inhaler technique and medication adherence before adding biologics 6

Sustained Efficacy

The DESTINATION study demonstrated that exacerbation reduction was sustained over 104 weeks of treatment, with consistent safety profile throughout the extended treatment period. 5 This long-term data supports tezepelumab as a durable treatment option for severe asthma requiring prolonged biologic therapy.