Tezepelumab-ekko (Tezspire)

Number: 1003

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Brand Selection for Medically Necessary Indications for Commercial Medical Plans

According to Aetna commercial benefit plans, health care services are considered not medically necessary if they are more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that member’s illness, injury or disease. Aetna commercial plans may require a trial of a lower-cost drug (preferred medication) that is at least as likely to produce equivalent therapeutic results before approving coverage for a higher-cost drug within the same therapeutic class. For a list of preferred drugs, refer to the Aetna Commercial Clinical Program Summary.

 

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses tezepelumab-ekko (Tezspire) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of tezepelumab-ekko (Tezspire) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tezepelumab-ekko (Tezspire), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies.  For information on site of service for tezepelumab-ekko (Tezspire), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Prescriber Specialties

   This medication must be prescribed by or in consultation with one of the following: 

   1. Asthma: an allergist/immunologist or pulmonologist; 
   2. Chronic rhinosinusitis with nasal polyps (CRSwNP): allergist/immunologist or otolaryngologist.

2. Criteria for Initial Approval

   Aetna considers tezepelumab-ekko (Tezspire) medically necessary for the treatment of the following indications:

   1. Asthma 

      1. For members 12 years of age or older who have previously received a biologic drug (e.g., Dupixent, Nucala) indicated for asthma in the past year; or
      2. For treatment of severe asthma when all of the following criteria are met:
         
         
         1. Member is 12 years of age or older; and
         2. Member has uncontrolled asthma as demonstrated by experiencing at least one of the following within the past year:
            
            
            1. Two or more asthma exacerbations requiring oral or injectable corticosteroid treatment; or
            2. One or more asthma exacerbation resulting in hospitalization or emergency medical care visit; or
            3. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma); and

         3. Member has inadequate asthma control despite current treatment with both of the following medications at optimized doses:

            1. High dose inhaled corticosteroid; and
            2. Additional controller (i.e., long acting beta₂-agonist, long acting muscarinic antagonists, leukotriene modifier, or sustained-release theophylline); and
               

         4. Member will continue to use maintenance asthma treatments (i.e., inhaled corticosteroid and additional controller) in combination with the requested medication; or

   2. Chronic rhinosinusitis with nasal polyps (CRSwNP)

      1. For members 12 years of age or older who have previously received a biologic drug (e.g., Nucala, Xolair, Dupixent) indicated for CRSwNP in the past year; or
      2. For treatment of CRSwNP in members 12 years of age or older when all of the following criteria are met:
         
         
         1. Member has bilateral nasal polyposis and chronic symptoms of sinusitis despite intranasal corticosteroid treatment for at least 4 weeks unless contraindicated or not tolerated; and
         2. Member has CRSwNP despite one of the following:
            
            
            1. Prior sino-nasal surgery; or
            2. Prior treatment with systemic corticosteroids within the last 2 years was ineffective, unless contraindicated or not tolerated; and

         3. Member has one of the following:

            1. A bilateral nasal endoscopy, anterior rhinoscopy, or computed tomography (CT) showing polyps reaching below the lower border of the middle turbinate or beyond in each nostril; or
            2. Meltzer Clinical Score of 2 or higher in both nostrils; or
            3. A total endoscopic nasal polyp score (NPS) of at least 5 with a minimum score of 2 for each nostril; and

         4. Member has symptoms of nasal blockage, congestion, or obstruction plus one of the following additional symptoms:

            1. Rhinorrhea (anterior/posterior); or
            2. Reduction or loss of smell; or
            3. Facial pain or pressure; and

         5. Member will continue to use a daily intranasal corticosteroid while being treated with the requested medication, unless contraindicated or not tolerated.

   Aetna considers all other indications as experimental, investigational, or unproven.

3. Continuation of Therapy

   Aetna considers continuation of tezepelumab-ekko (Tezspire) therapy medically necessary for the treatment of the following indications:

   1. Asthma - for treatment of severe asthma when all of the following criteria are met:
      
      
      1. Member is 12 years of age or older; and
      2. Asthma control has improved on the requested medication as demonstrated by at least one of the following:
         
         
         1. A reduction in the frequency and/or severity of symptoms and exacerbations; or
         2. A reduction in the daily maintenance oral corticosteroid dose; and
            

      3. Member will continue to use maintenance asthma treatments (i.e., inhaled corticosteroid and additional controller) in combination with the requested medication; or

   2. Chronic rhinosinusitis with nasal polyps (CRSwNP) - for treatment of CRSwNP in members 12 years of age or older when both of the following are met:

      1. Member has achieved or maintained a positive clinical response with the requested medication as evidenced by improvement in signs and symptoms of CRSwNP (e.g., improvement in nasal congestion, nasal polyp size, loss of smell, anterior or posterior rhinorrhea, sino-nasal inflammation, hyposmia or facial pressure or pain, reduction in corticosteroid use); and
      2. Member will continue to use a daily intranasal corticosteroid while being treated with the requested medication, unless contraindicated or not tolerated.

4. Other

   For all indications: Member cannot use the requested medication concomitantly with any other biologic drug or targeted synthetic drug for the same indication.

   Note: If the member is a current smoker or vaper, they should be counseled on the harmful effects of smoking and vaping on pulmonary conditions and available smoking and vaping cessation options.

5. Related Policies

   1. CPB 0059 - Peak Flow Meters
   2. CPB 0670 - Omalizumab (Xolair)
   3. CPB 0897 - Mepolizumab (Nucala)
   4. CPB 0907 - Reslizumab (Cinqair)
   5. CPB 0925 - Benralizumab (Fasenra)

Dosage and Administration

Tezspire is supplied for injection as 210 mg of tezepelumab-ekko in 1.91 mL (110 mg/mL) solution in a single-dose glass vial, pre-filled syringe, and a pre-filled pen. 

The recommended dosage of Tezspire is 210 mg once every 4 weeks administered subcutaneously. Tezspire vial and pre-filled syringe are intended for administration by a healthcare provider. The pre-filled pen can be self-administered or administered by caregivers or healthcare providers.

Source: Amgen, 2025

Experimental, Investigational, or Unproven

Aetna considers tezepelumab experimental, investigational, or unproven for the following indications (not an all-inclusive list) because the safety and/or effectiveness for these indications has not been established:

1. Allergic broncho-pulmonary aspergillosis
2. Combined tezepelumab and allergen immunotherapy for the treatment of allergic rhinitis.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
30000-31299	Nose and Accessory sinuses [sino-nasal surgery]
31231	Nasal endoscopy, diagnostic, unilateral or bilateral (separate procedure)
31233	with maxillary sinusoscopy (via inferior meatus or canine fossa puncture)
31235	with sphenoid sinusoscopy (via puncture of sphenoidal face or cannulation of ostium)
70486-70488	Computed tomography, maxillofacial area
95115 - 95199	Allergen immunotherapy
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
HCPCS codes covered if selection criteria are met:
J2356	Injection, tezepelumab-ekko, 1 mg
Other HCPCS codes related to the CPB:
Dupixent-no specific code
J0517	Injection, benralizumab, 1 mg
J0702	Injection, betamethasone acetate 3 mg and betamethasone sodium phosphate 3 mg
J1010	Injection, methylprednisolone acetate, 1 mg
J1020	Injection, methylprednisolone acetate, 20 mg
J1030	Injection, methylprednisolone acetate, 40 mg
J1040	Injection, methylprednisolone acetate, 80 mg
J1100	Injection, dexamethasone sodium phosphate, 1 mg
J1700	Injection, hydrocortisone acetate, up to 25 mg
J1710	Injection, hydrocortisone sodium phosphate, up to 50 mg
J1720	Injection, hydrocortisone sodium succinate, up to 100 mg
J2182	Injection, mepolizumab, 1 mg
J2357	Injection, omalizumab, 5 mg
J2650	Injection, prednisolone acetate, up to 1 ml
J2786	Injection, reslizumab, 1 mg
J2810	Injection, theophylline, per 40 mg
J2919	Injection, methylprednisolone sodium succinate, 5 mg
J2920	Injection, methylprednisolone sodium succinate, up to 40 mg
J2930	Injection, methylprednisolone sodium succinate, up to 125 mg
J3299-J3304	Injection, triamcinolone
J7509	Methylprednisolone oral, per 4 mg
J7510	Prednisolone oral, per 5 mg
J7512	Prednisone, immediate release or delayed release, oral, 1 mg
J7606	Formoterol fumarate, inhalation solution, fda approved final product, non-compounded, administered through dme, unit dose form, 20 micrograms
J7607	Levalbuterol, inhalation solution, compounded product, administered through dme, concentrated form, 0.5 mg
J7609	Albuterol, inhalation solution, compounded product, administered through dme, unit dose, 1 mg
J7610	Albuterol, inhalation solution, compounded product, administered through dme, concentrated form, 1 mg
J7611	Albuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, 1 mg
J7612	Levalbuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, 0.5 mg
J7613	Albuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose, 1 mg
J7614	Levalbuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose, 0.5 mg
J7615	Levalbuterol, inhalation solution, compounded product, administered through dme, unit dose, 0.5 mg
J7620	Albuterol, up to 2.5 mg and ipratropium bromide, up to 0.5 mg, fda-approved final product, non-compounded, administered through dme
J7622	Beclomethasone, inhalation solution, compounded product, administered through dme, unit dose form, per milligram
J7626-J7627	Budesonide, inhalation solution
J7631-J7632	Cromolyn sodium, inhalation solution
J7633-J7634	Budesonide, inhalation solution
J7637-J7638	Dexamethasone, inhalation solution
J7640	Formoterol, inhalation solution, compounded product, administered through dme, unit dose form, 12 micrograms
J7641	Flunisolide, inhalation solution, compounded product, administered through dme, unit dose, per milligram
J7644-J7645	Ipratropium bromide, inhalation solution
J7657-J7660	Isoproterenol hcl, inhalation solution
J7667-J7670	Metaproterenol sulfate, inhalation solution
J7677	Revefenacin inhalation solution, fda-approved final product, non-compounded, administered through DME, 1 microgram
J7683-J7684	Triamcinolone, inhalation solution
J8540	Dexamethasone, oral, 0.25 mg
J8541	Dexamethasone (hemady), oral, 0.25 mg
S2342	Nasal endoscopy for post-operative debridement following functional endoscopic sinus surgery, nasal and/or sinus cavity(s), unilateral or bilateral
ICD-10 codes covered if selection criteria are met:
J32.0-J32.9	Chronic sinusitis
J33.0-J33.9	Nasal polyp
J45.50 - J45.52	Severe persistent asthma
ICD-10 codes not covered for indications listed in the CPB:
B44.81	Allergic bronchopulmonary aspergillosis
J30.1 – J30.9	Allergic rhinitis

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma
• Add-on maintenance treatment of adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP)

Limitations of use: Not for the relief of acute bronchospasm or status asthmaticus.

Tezepelumab-ekko, branded as Tezspire (Amgen Inc.), is a thymic stromal lymphopoietin (TSLP) blocker and a human monoclonal antibody (IgG2λ) that binds to human TSLP with a dissociation constant of 15.8 pM, effectively blocking its interaction with the heterodimeric TSLP receptor. TSLP, primarily produced by epithelial cells, plays a crucial role in airway and mucosal inflammation, which are key factors in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). This inflammation involves various cell types, including mast cells, eosinophils, neutrophils, macrophages, lymphocytes, and ILC2 cells, as well as several mediators such as histamine, eicosanoids, leukotrienes, and cytokines. Increased levels of TSLP mRNA and protein have been observed in the airways of patients with asthma and in nasal polyp tissue. By inhibiting TSLP, tezepelumab-ekko reduces levels of biomarkers and cytokines associated with inflammation, including blood eosinophils, airway submucosal eosinophils, IgE, FeNO, IL-5, and IL-13; however, the precise mechanism by which tezepelumab-ekko exerts its effects in asthma and CRSwNP has not been definitively established.

The labeled warnings and precautions for Tezspire include several important considerations for patients and healthcare providers. Hypersensitivity reactions, such as rash and allergic conjunctivitis, have been observed in clinical trials, with postmarketing reports of anaphylaxis; these reactions can occur shortly after administration or may have a delayed onset. Tezspire is not intended for the treatment of acute asthma symptoms or exacerbations, and patients should seek medical advice if their condition worsens after starting treatment. Additionally, systemic or inhaled corticosteroids should not be discontinued abruptly when initiating Tezspire therapy; any reduction in corticosteroid dosage should be gradual and supervised by a physician to avoid withdrawal symptoms. There is also a risk related to helminth infections, as TSLP may play a role in the immune response to these infections; patients with known helminth infections should be treated before starting Tezspire, and treatment should be discontinued if a new infection occurs and does not respond to anti-helminth therapy. Lastly, the use of live attenuated vaccines in conjunction with Tezspire has not been studied, so such vaccines should be avoided in patients receiving this treatment.

There are currently no available data on the use of Tezspire in pregnant women to assess the risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Monoclonal antibodies like tezepelumab-ekko are known to have greater placental transfer during the third trimester, which may increase potential effects on the fetus during this period. An enhanced pre- and post-natal development study in cynomolgus monkeys showed placental transport of tezepelumab-ekko without evidence of fetal harm at doses significantly higher than the maximum recommended human dose. The background risk of major birth defects and miscarriages in the general U.S. population is estimated to be 2% to 4% and 15% to 20%, respectively. Additionally, women with poorly or moderately controlled asthma face increased risks of preeclampsia, prematurity, low birth weight, and small for gestational age neonates, highlighting the importance of closely monitoring asthma control and adjusting treatment as necessary during pregnancy. Moreover, there is currently no information available regarding the presence of tezepelumab-ekko in human milk, its effects on breastfed infants, or its impact on milk production. However, as a human monoclonal antibody immunoglobulin G2λ (IgG2λ), it is known that immunoglobulin G (IgG) is present in small amounts in human milk. In studies with cynomolgus monkeys, tezepelumab-ekko was detected in milk postpartum after administration during pregnancy. When considering the use of Tezspire during lactation, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant from Tezspire or the underlying maternal condition.

The most common adverse reactions associated with Tezspire, occurring in at least 3% of patients, include various symptoms for different conditions. In patients with asthma, the most frequently reported adverse reactions are pharyngitis, arthralgia, and back pain. For those with chronic rhinosinusitis with nasal polyps (CRSwNP), common adverse reactions include nasopharyngitis, upper respiratory tract infection, epistaxis, pharyngitis, back pain, influenza, injection site reactions, and arthralgia.

Asthma

Asthma is chronic, heterogenous condition that is usually associated with airway inflammation and bronchial hyperresponsiveness which results in narrowing of the airways, leading to less airflow to the lungs. Airway swelling or inflammation can be triggered by several factors, including allergens or irritant exposure and viral infections. Respiratory symptoms, "asthma attack" exacerbation, may include wheeze, chest tightness, shortness of breath, and/or cough, which can vary in frequency and intensity over time. Airflow limitation may later become persistent and severe (GINA, 2021; FDA, 2021).

According to the Global Initiative for Asthma (GINA) (2021), severe asthma is defined as asthma that is uncontrolled despite high dose inhaled corticosteroid (ICS)-long-acting beta₂ agonist (LABA), or that requires high dose ICS-LABA to remain controlled. "Severe asthma attacks can be intense, last for long periods of time, and impact daily activities. Severe asthma symptoms usually do not get better with use of short-term treatments. Approximately 5-10 percent of Americans with asthma have severe asthma" (FDA, 2021).

On December 20, 2021, the FDA announced the approval of the first asthma treatment targeting thymic stromal lymphopoietin (TSLP). Tezspire (tezepelumab-ekko), a TSLP blocker, human monoclonal antibody (IgG2λ), was approved as an add-on maintenance treatment used to improve severe asthma symptoms when used with a patient’s current asthma medicine. Tezspire is approved for adults and children aged 12 years and older with severe asthma not controlled by their current asthma medicine. Tezspire is also the first treatment for severe asthma that is not limited to a specific type of severe asthma. Tezspire is administered once every four weeks as a subcutaneous injection by a health care professional.

FDA approval as based on the safety and efficacy in two randomized, double-blind, parallel group, placebo-controlled clinical trials (PATHFINDER, NCT02054130; NAVIGATOR, NCT03347279) in which patients receiving Tezspire had significant reductions in the annualized rate of asthma attacks compared to placebo. Additionally, there were fewer asthma attacks requiring emergency room visits and/or hospitalization among patients treated with Tezspire compared to placebo. The benefits of Tezspire seen in patients weren’t limited by specific severe asthma type (FDA, 2021).

Corren et al (2021) state that in the phase 2b PATHWAY study, tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo. Adults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Inclusion criteria required documented physician-diagnosed asthma. Patients must have received a physician-prescribed asthma controller regimen with medium- or high-dose inhaled corticosteroids (ICS) plus long acting β2 agonist (LABA). If on asthma controller medications in addition to ICS plus LABA, the dose of the other asthma controller medications (leukotriene receptor inhibitors, theophylline, secondary ICS, long-acting anti-muscarinics (LAMA), cromones, or maintenance oral prednisone or equivalent up to a maximum of 10 mg daily or 20 mg every other day for the maintenance treatment of asthma) must be stable. Patients must have a documented history of at least 2 asthma exacerbation events or at least 1 severe asthma exacerbation resulting in hospitalization within the 12 months prior to first study visit. Patient-reported outcomes (PROs) were assessed using the asthma control questionnaire-6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity. Overall, 550 patients were randomized. The authors found that up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity. The authors concluded that tezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.

Menzies-Gow et al (2021) conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NAVIGATOR). Patients (12 to 80 years of age; n=1061) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. Inclusion criteria required patients, aged 12 to 80 years, to have documented physician-diagnosed asthma for at least 12 months, have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months, documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months, have at least one additional maintenance asthma controller medication according to standard practice of care for at least 3 months, morning pre-BD FEV1 <80% predicted normal (<90% for subjects 12-17 years), evidence of asthma as documented by either: documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months or post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening, documented history of at least 2 asthma exacerbation events within 12 months, and have an ACQ-6 score ≥1.5 at screening and on day of randomization. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire-6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]). Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; p<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (p<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (p<0.001) and scores on the ACQ-6 (p<0.001), AQLQ (p<0.001), and ASD (p = 0.002). The frequencies and types of adverse events did not differ meaningfully between the two groups. The authors concluded that patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. 

Laidlaw and colleagues (2023) investigated the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in the phase 3 NAVIGATOR study (NCT03347279). A total of 1,059 patients with severe asthma were randomly assigned in a 1:1 ratio to receive either tezepelumab 210 mg or a placebo, administered subcutaneously every four weeks for 52 weeks. The prespecified exploratory analyses focused on annualized asthma exacerbation rates (AAER) over the 52-week period, as well as changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in one second, Sino-Nasal Outcome Test (SNOT)-22 scores, and outcomes related to asthma control and health-related quality of life (HRQoL) in subgroups with nasal polyps (NPs). Additionally, post hoc assessments were conducted to evaluate changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum levels of interleukins (IL)-5, IL-6, IL-8, and IL-13. The authors found that tezepelumab led to an 85% reduction in annualized asthma exacerbation rates (AAER) over 52 weeks compared to placebo in patients with nasal polyps (NPs) (95% confidence interval [CI]: 72, 92; n=118) and a 51% reduction in those without NPs (95% CI: 40, 60; n=941). By week 52, patients receiving tezepelumab showed improvements in lung function, asthma control, and health-related quality of life (HRQoL) compared to those on placebo, regardless of NP status. In patients with NPs, tezepelumab also significantly decreased SNOT-22 total scores at 28 weeks (-12.57 points [-19.40, -5.73]) and 52 weeks (-10.58 points [-17.75, -3.41]). Additionally, at week 52, tezepelumab was associated with reductions in blood eosinophil counts, as well as levels of FeNO, IgE, IL-5, IL-13, EDN, and MMP-10 compared to placebo, irrespective of whether patients had NPs. The authors concluded that tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.

Updated GINA 2024 guidelines now recommend the use of inhaled corticosteroid-containing medications as maintenance and reliever therapy (MART). GINA has recommended against the use of regular SABA-only therapy since 2019 due to increased airway hyperresponsiveness, diminished bronchodilator effect, and increased eosinophilia.

A 2024 GINA update advises that "all adults and adolescents with asthma receive inhaled corticosteroid (ICS)-containing medication and should not be treated with short acting beta agonist (SABA) alone. The 2024 GINA strategy divides treatment into two 'Tracks": Track 1 (preferred Track), the reliever is as-needed combination low dose ICS-formoterol; Track 2 uses SABA as the reliever along with a separate ICS inhaler. The updates also stress the importance that individuals with asthma should have a written asthma action plan, and asthma management should be tailored to the individual to help reduce the occurrence of serious exacerbations, fatalities, and hospitalizations" (Dubin et al, 2024).

The 2024 GINA update states to consider add-on targeted biologic therapy for patients with exacerbations or poor symptom control on high dose ICS-LABA who have evidence of Type 2 inflammation, characterized by elevated eosinophils or increased fractional exhaled nitric oxide, and it may be accompanied by atopy and elevated IgE. The guidelines recommend an add-on Type 2 targeted biologic for patients with exacerbations and/or poor symptom control despite taking at least high-dose ICS-LABA, and who have allergic or eosinophilic biomarkers or need maintenance oral corticosteroids. 

Maintenance treatment includes medications to be used continuously, even when the person does not have asthma symptoms. Examples include ICS-containing medications (ICS, ICS-LABA, ICS-LABA-LAMA), as well as LTRA (leukotriene receptor antagonist) and biologic therapy. Treatment regimen in which the patient uses an ICS-formoterol inhaler every day (maintenance dose) and also uses the same medication as needed for relief of asthma symptoms (reliever doses), is referred to as maintenance-and-reliever therapy (MART) (GINA, 2024).

Allergic Broncho-Pulmonary Aspergillosis

Ogata et al (2023) reported on the case of an 82-year-old man who had been diagnosed with asthma.  He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated.  The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain . In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) was established.  The patient underwent treatment with tezepelumab.  Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms.  The authors concluded that tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are needed to validate these findings.

Chronic Rhinosinusitis with Nasal Polyps

Chiang and Lee (2023) stated that epithelial barrier disturbances in patients with chronic rhinosinusitis with nasal polyps play an important role in both the innate and adaptive immune responses, contributing to chronic inflammation, olfactory dysfunction, and impairments in quality of life (QOL).  These researchers examined the role of the sinonasal epithelium in disease and health, reviewed the pathophysiology of epithelial barrier dysfunction in CRSwNP, and the immunologic targets for treatment.  Blockade of cytokines such as thymic stromal lymphopoietin (TSLP), IL-4, and IL-13 have shown promise in barrier restoration and IL-13, specifically may be central to olfactory dysfunction.  The authors concluded that the sinonasal epithelium plays a crucial role in the health and function of the mucosa and immune response.  Increased understanding of the local immunologic dysfunction has led to several therapeutics that can potentially restore epithelial barrier function and olfaction.  Real world and comparative effectiveness studies are needed.  Tezepelumab is one of the key words in this literature review.

In the Phase III WAYPOINT trial, Lipworth et al. (2025) evaluated the efficacy and safety of add-on tezepelumab in adults with severe, uncontrolled CRSwNP. WAYPOINT was a double-blind, multicenter, randomized, placebo-controlled, parallel group trial that included a total of 408 adults with physician-diagnosed, symptomatic severe CRSwNP, who were assigned to receive either tezepelumab (210 mg; n=203) or placebo (n=205) subcutaneously every four weeks for 52 weeks, alongside standard care. The co-primary endpoints were changes from baseline in the total nasal-polyp score (range, 0 to 4 for each nostril; higher scores indicate greater severity) and the mean nasal-congestion score (range, 0 to 3; higher scores indicate greater severity) at week 52. The authors found that at week 52, the tezepelumab group showed significant improvements in the total nasal-polyp score (mean difference vs. placebo, -2.07; 95% confidence interval [CI], -2.39 to -1.74) and the mean nasal-congestion score (mean difference, -1.03; 95% CI, -1.20 to -0.86), with P-values less than 0.001 for both. Additionally, tezepelumab significantly improved the loss-of-smell score (mean difference vs. placebo, -1.00; 95% CI, -1.18 to -0.83), the total score on the Sinonasal Outcome Test (SNOT-22; range, 0 to 110; higher scores indicate greater severity) with a mean difference of -27.26 (95% CI, -32.32 to -22.21), the Lund-Mackay score (range, 0 to 24; higher scores indicate greater severity) with a mean difference of -5.72 (95% CI, -6.39 to -5.06), and the total symptom score (range, 0 to 24; higher scores indicate greater severity) with a mean difference of -6.89 (95% CI, -8.02 to -5.76), all with P-values under 0.001. Furthermore, only 0.5% of patients in the tezepelumab group required nasal polyp surgery compared to 22.1% in the placebo group (hazard ratio, 0.02; 95% CI, 0.00 to 0.09), and the use of systemic glucocorticoids was significantly lower in the tezepelumab group (5.2%) than in the placebo group (18.3%) (hazard ratio, 0.12; 95% CI, 0.04 to 0.27), with P-values less than 0.001 for both time-to-event analyses. The authors concluded that these findings demonstrate that tezepelumab therapy led to significant reductions in nasal polyp size, nasal congestion severity, sinonasal symptoms, and the need for surgical intervention or systemic glucocorticoids compared to placebo.

In October 2025, the FDA approved Tezspire for the add-on maintenance treatment of adult and paediatric patients aged 12 years and older with uncontrolled CRSwNP. Approval was based on the efficacy and safety outcomes from the WAYPOINT Phase III trial, presented at the 2025 American Academy of Allergy Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, which found statistically significant efficacy for the co-primary endpoints of improvement in total nasal polyp score and in bi-weekly mean nasal congestion score at Week 52.

Combined Tezepelumab and Allergen Immunotherapy for the Treatment of Allergic Rhinitis

Corren et al (2023) stated that TSLP has been shown to play a central role in the initiation and persistence of allergic responses.  In a double-blind, parallel design study, these researchers examined if Tezepelumab would improve the effectiveness of subcutaneous allergen immunotherapy (SCIT) and promote the development of tolerance in patients with allergic rhinitis.  A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation.  Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study.  At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUC0-1h] and as peak score [Peak0-1h] during the 1st hour following NAC) were significantly reduced in patients receiving tezepelumab/SCIT compared to SCIT alone.  At week 104, 1 year after stopping treatment, the primary endpoint TNSS AUC0-1h was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS Peak0-1h was significantly lower in those receiving combination treatment versus SCIT.  Transcriptomic analysis of nasal epithelial samples showed that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent down-regulation of a gene network related to type 2 inflammation that was associated with improvement in NAC responses.  The authors concluded that inhibition of TSLP augmented the effectiveness of SCIT during therapy and may promote tolerance after a 1-year course of treatment.

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