Observational Study on the Clinical Profile of Patients With Uncontrolled Severe Asthma Treated With Tezepelumab in Italy

There is a current need to gain information on the clinical profile of patients eligible for treatment with Tezepelumab according to the approved and reimbursed indication in Italy. Moreover, being Tezepelumab the latest approved biologic drug for severe asthma, it is important to better understand clinical response to treatment in patients with high severe asthma burden as: patients with allergic-eosinophilic phenotype; patients with low eosinophils level; patients affected by severe asthma associated with sinonasal disease; biologic-naïve patients, as well as bio-treated patients. The present observational study aims at filling the above-mentioned knowledge gaps in the study population in terms of clinical course, disease control and clinical remission, use of healthcare resources (treatments, visits, hospitalizations), lung functions, biomarkers, and sinonasal outcomes.

• Tezepelumab (Biological): Tezepelumab is indicated as an add-on maintenance treatment in adult and adolescent ≥12 years patients with severe uncontrolled asthma despite high-dose inhaled corticosteroids plus long-acting β-agonists

Primary outcomes

• Demographic and Clinic characterization [Basal]: To describe demographic and clinical characteristics of a population of patients with severe asthma who initiated treatment with tezepelumab
• COMORBIDITIES AND RELEVANT MEDICAL HISTORY [Basal]: To describe the respiratory and non-respiratory related conditions in patients with severe asthma who initiated treatment with tezepelumab

Secondary outcomes

• Exacerbation rate [Basal, 12 months, 24 months]: To describe the annualized asthma exacerbation rate in the 12-month period before (baseline period) and up to 12 and 24-months (follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• mOCS (maintenance Oral Corticosteroids) and ICS (Inhaled Corticosteroids) use [Basal, 12 months, 24 months]: To describe the mOCS and ICS daily dose in the 12-month period before (baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma
• ACT (Asthma Control Test) score [Basal, 12 months, 24 months]: To describe asthma control (ACT score) from last ACT score recorded before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma. ACT score range 1-25 - 25 means sympthoms under control
• Asthma Control Questionnaire (ACQ) score [Basal, 12 months, 24 months]: To describe ACQ score from last score recorded before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma. ACQ score range 0-6. 6 means severely uncontrolled
• Lung function FEV1 (L) [Basal, 12 months, 24 months]: To describe lung function through FEV1 (Forced Expiratory Volume in 1 Second) from last measurement before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Lung function FVC (L) [Basal, 12 months, 24 months]: To describe lung function through FVC (Forced vital capacity) from last measurement before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Lung function % predicted FVC [Basal, 12 months, 24 months]: To describe lung function through % predicted FVC (Forced vital capacity) from last measurement before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Lung function % predicted FEV1 [Basal, 12 months, 24 months]: To describe lung function through % predicted FEV1 (Forced expiratory volume in 1 second) from last measurement before index date (within 12-month baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Biomarkers - BEC (blood eosinophils count) [Basal, 12 months, 24 months]: To describe BEC (cells/microL (cells/mm3)) in the 12-month period before (baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Biomarkers - FeNO (Fractional exhaled Nitric Oxide) [Basal, 12 months, 24 months]: To describe FeNO (ppb) in the 12-month period before (baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma. FeNo range 0-99
• Biomarkers - IgE (Immunoglobulin E) [Basal, 12 months, 24 months]: To describe blood IgE (IU/mL) in the 12-month period before (baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Treatments [Basal, 12 months, 24 months]: To describe treatment of asthma in 12-month period before (baseline period) and up to 12 and 24-months (+/- 2 months, follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• Clinical Remission [12 months, 24 months]: To describe frequency and characteristics of patients achieving partial and complete clinical remission after 12 months and 24 months of treatment (+/- 2 months) \[Severe Asthma Network in Italy (SANI) 2023 definition\] \[Canonica G et al, 2023\].

Other outcomes

• Demographics and clinic characterization_clinic remission [12 months, 24 months]: To describe baseline demographics and clinical characteristics associated with clinical remission, frequency and characteristics of tezepelumab-treated patients achieving clinical remission after 12 and 24 months.
• HCRU - number of specialistic visits for asthma [Basal, 12 months, 24 months]: To describe total number of specialist visits for asthma in the 12-month period before (baseline period) and up to 12 and 24-months (follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• HCRU - number of hospitalization [Basal, 12 months, 24 months]: To describe total number of hospitalization the 12-month period before (baseline period) and up to 12 and 24-months (follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• HCRU - number of ER visits [Basal, 12 months, 24 months]: To describe total number of ER visits in the 12-month period before (baseline period) and up to 12 and 24-months (follow-up period) after initiating treatment with tezepelumab in patients with severe asthma.
• NP clinical outcomes - NPS (Nasal Polyp Score) [Basal, 12 months, 24 months]: To describe NPS (0-8) among severe asthma patients with comorbid CRSwNP during the baseline and follow-up period (12 and 24 months of treatment). NPS score: reduced score indicates improvement
• NP clinical outcomes - Lund-Mackay (LMK) score [Basal, 12 months, 24 months]: To describe LMK (0-24) among severe asthma patients with comorbid CRSwNP during the baseline and follow-up period (12 and 24 months of treatment). LMK 24 means complete opacity of all sinuses
• NP clinical outcomes - Visual Analogue Scale (VAS) [Basal, 12 months, 24 months]: To describe VAS (0-40) among severe asthma patients with comorbid CRSwNP during the baseline and follow-up period (12 and 24 months of treatment). VAS 40 means higher pain
• NP clinical outcomes - 22-item Sino-Nasal Outcome Test (SNOT-22) [Basal, 12 months, 24 months]: To describe SNOT-22 (0-110) among severe asthma patients with comorbid CRSwNP during the baseline and follow-up period (12 and 24 months of treatment). Higher scores indicate greater rhinosinusitis-related health burden
• NP clinical outcomes - NP surgeries [Basal, 12 months, 24 months]: To describe number of NP surgeries among severe asthma patients with comorbid CRSwNP during the baseline and follow-up period (12 and 24 months of treatment). Higher scores indicate greater rhinosinusitis-related health burden
• Subgroups [Basal, 12 months, 24 months]: To describe clinical outcomes from the primary, secondary, and/or exploratory objectives in sub-groups of interest
• Tezepelumab treatment [12 months, 24 months]: To describe duration of therapy with tezepelumab, discontinuation, and reasons for discontinuation after initiating treatment with tezepelumab.

Sex: All, ages: 12 Years to 120 Years

Inclusion Criteria:

1. Adult and adolescent patients (age ≥12 years) at the Index Date (i.e., first administration of tezepelumab);
2. Patients with severe uncontrolled asthma (diagnosed according to clinician's judgment as per ERS-ATS or GINA guidelines) requiring a stable treatment of high doses of ICS and a long acting β2 agonist ± additional asthma controller;
3. Patients who received at least one injection of tezepelumab from February 2024 to March 2025 , according to Italian reimbursement indications;
4. Patients who signed the ICF and privacy form.
5. Patients with continuous enrolment in the data source for at least 12-months before the index date.
6. Patients with at least three months of continuous enrolment in the data source after the index date.

Exclusion Criteria:

1. Patients with hypersensitivity to the active ingredient or any of the excipients of Tezspire;
2. Patients who received any biologic drug for the treatment of asthma in a clinical trial at any time during the 12-months prior to the index date.
3. Patients who, during the observation period, participated in studies imposing a specific patient's management strategy, which does not correspond to the site's normal clinical practice.