Clinical Benefits of Tezepelumab in a Real-World Cohort of Patients With Severe Uncontrolled Asthma in Castilla-La Mancha, Spain

Abstract

Introduction

Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody approved for the treatment of severe uncontrolled asthma regardless of inflammatory phenotype. Although its efficacy has been demonstrated in clinical trials, there is a growing need to evaluate its effectiveness in real-world clinical practice in Spain. The aim of this study was to evaluate the clinical impact of tezepelumab in patients with severe asthma treated in 5 hospitals in Castilla-La Mancha, Spain.

Material and methods

This was a retrospective multicenter observational study. Adult patients with severe asthma treated with tezepelumab were included between January 2023 and April 2025. Clinical, functional, and laboratory parameters were evaluated between the 6-month baseline period (before treatment initiation) and the follow-up visit. Exacerbations, asthma control test (ACT), lung function (forced expiratory volume in 1 second [FEV₁]), use of oral corticosteroids, and eosinophil count were analyzed.

Results

A total of 48 patients were included (mean age 52.8 years; 70.8% women). The mean number of exacerbations decreased significantly from 2.06 to 0.22 per patient (p < 0.001), ACT scores increased from 12.8 to 19.2 points (p < 0.001), FEV₁ improved by 170 mL (p = 0.01), and chronic use of oral corticosteroids fell from 14.5% to 4.2%. No significant differences were observed in inflammatory phenotype or prior history of biological treatment, except for a greater reduction in oral corticosteroid cycles in biologic-naïve patients. Clinical remission was achieved in 25% of patients.

Conclusions

Tezepelumab was shown to be effective in real-world clinical practice, achieving a significant improvement in severe asthma control and lung function, while reducing exacerbations and oral corticosteroid use.

Resumen

Introducción

Tezepelumab es un anticuerpo monoclonal anti–linfopoyetina estromal tímica aprobado para el tratamiento del asma grave no controlada, independientemente del fenotipo inflamatorio. Aunque su eficacia se ha demostrado en ensayos clínicos, es necesario evaluar su efectividad en la práctica clínica real en España. Este estudio evaluó el impacto clínico de tezepelumab en pacientes con asma grave atendidos en cinco hospitales de Castilla-La Mancha.

Material y métodos

Estudio observacional retrospectivo y multicéntrico. Se incluyeron pacientes adultos con asma grave tratados con tezepelumab entre enero de 2023 y abril de 2025. Se compararon parámetros clínicos, funcionales y analíticos entre los 6 meses previos al inicio del tratamiento y la visita de seguimiento. Se analizaron exacerbaciones, test de control del asma (ACT), función pulmonar (volumen espiratorio forzado en el primer segundo [FEV₁]), uso de corticosteroides orales y recuento de eosinófilos.

Resultados

Se incluyeron 48 pacientes (edad media 52,8 años; 70,8% mujeres). Las exacerbaciones disminuyeron de 2,06 a 0,22 por paciente (p< 0,001). Las puntuaciones del ACT aumentaron de 12,8 a 19,2 puntos (p< 0,001), el FEV₁ mejoró 170 mL (p = 0,01) y el uso crónico de corticosteroides orales se redujo del 14,5% al 4,2%. No hubo diferencias relevantes según fenotipo inflamatorio o tratamiento biológico previo, salvo mayor reducción de ciclos de corticosteroides en pacientes naïve al tratamiento biológico. El 25% alcanzó remisión clínica.

Conclusiones

Tezepelumab resultó efectivo en la práctica clínica real, mejorando el control del asma grave y la función pulmonar, y reduciendo exacerbaciones y el uso de corticosteroides orales.

Introduction

Asthma, a chronic disease that affects about 334 million people worldwide, carries a significant social and health burden.¹ In Spain, its prevalence is approximately 5% in the adult population and 10% in the pediatric population.² Although most patients have mild or moderate disease, it is estimated that between 6% and 10% develop severe asthma.² This is defined by a need for maintenance treatment with high-dose inhaled corticosteroids (ICS) combined with long-acting bronchodilators (LABA). Other drugs, such as antileukotrienes, anticholinergics, and, in some cases, oral corticosteroids (OCS), are often required for disease control.^1,2

Despite intensive multi-drug treatment, many patients with severe asthma have uncontrolled disease, characterized by frequent exacerbations, persistent airflow obstruction, and significant loss of quality of life.^1,2 This subgroup is also associated with a disproportionately high use of healthcare resources, accounting for almost half of the total expenditure allocated to asthma.² In recent years, growing knowledge of the immunopathogenesis of asthma has helped establish more precise phenotypes. In inflammatory terms, 2 large groups are recognized: type 2 (T2) asthma, present in allergic and eosinophilic asthma, and non-T2 asthma. In clinical practice, three different phenotypes of severe uncontrolled asthma with therapeutic implications are distinguished: T2 allergic asthma, T2 eosinophilic asthma and non-T2 asthma. However, T2 phenotypes often show some degree of overlap.² This classification has facilitated the development of biological treatments aimed at specific inflammatory targets.

Against this background, tezepelumab, a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP) – an upstream cytokine involved in multiple inflammatory pathways – has recently been introduced for use in Spain.³ Unlike other biologics, tezepelumab has shown efficacy not only in patients with T2 asthma, but also in individuals without standard inflammatory markers, thus expanding its range of indications.^3–5 However, while clinical trials have shown promising results in terms of reducing exacerbations and improving disease control, data from observational studies conducted in real-world clinical practice conditions in Spain remain scant.

To help address this gap, we designed a multicenter study to evaluate tezepelumab effectiveness in real-world clinical practice conditions. This cohort provides a distinctive contribution by offering multicenter real-world data from a Spanish region, reflecting routine practice and allowing subgroup analyses according to inflammatory phenotype and previous biologic treatment. The aim was to analyze the clinical response to tezepelumab in patients with severe asthma treated in hospital respiratory medicine departments in Castilla-La Mancha, Spain, and to identify baseline characteristics potentially associated with a better therapeutic response. Such knowledge would help optimize candidate selection, avoid unnecessary treatments, and offer cost-effective improvement of health outcomes. To this end, we compared clinical and functional effectiveness before (≤6 month baseline period) and after administration of the biological drug.

Material and methods

Objectives

The primary objective was to evaluate the clinical benefits of tezepelumab in real-world clinical practice at the first follow-up visit, in terms of exacerbations, asthma control test (ACT) score, OCS use, lung function (determined by forced expiratory volume in 1 second [FEV₁]), and eosinophil levels.

Secondary objectives included analysis of the impact of tezepelumab by subgroups, determined according to inflammatory phenotype (T2 vs non-T2) and prior history of monoclonal antibody treatment (naïve vs non-naïve patients), and evaluation of the proportion of patients who achieved clinical remission.

Study design

This was a real-world, observational, retrospective multicenter study carried out in 5 hospitals in the region of Castilla-La Mancha, Spain (Hospital General Universitario de Ciudad Real, Hospital Universitario de Toledo, Complejo Hospitalario Universitario de Albacete, Hospital de Universitario de Guadalajara, and Hospital Nuestra Señora del Prado de Talavera). We included all severe asthmatic patients over 18 years of age treated with tezepelumab in severe asthma units or dedicated asthma clinics within respiratory medicine departments. Patients who initiated tezepelumab between January 2023 and April 2025 were eligible. Data were retrospectively obtained from electronic medical records at the participating centers and entered into a shared regional severe asthma registry using an electronic case report form (e-CRF), to ensure standardized data capture across centers.

All patients were diagnosed with asthma based on a compatible clinical history along with bronchodilator spirometry (FEV₁ reversibility ≥12%, positive methacholine/mannitol test or FEV₁ variability ≥20%). These patients were receiving maintenance treatment, consisting of a combination of high-dose ICS/LABA/long-acting muscarinic antagonist (LAMA), according to GEMA 5.3 criteria (version in force at the time of patient inclusion) for severe uncontrolled asthma.⁶ The information obtained by each pulmonologist was recorded in an e-CRF, accessible on the ALCEINGENIERA platform. Each case was identified by an encrypted code, generated by the system itself. All data recorded in the e-CRF were stored on a central server and handled according to applicable data protection regulations, guaranteeing confidentiality and security.

Demographic data, phenotype, comorbidities, previous treatment with another biological drug, corticosteroid dependence (defined as the daily use of systemic corticosteroids for at least 6 months), asthma control measured by ACT, percentage of predicted FEV₁ (FEV₁%), and blood eosinophil count were collected at the initiation of biological therapy. To assess the effectiveness of the treatment, these parameters were compared between the pretreatment visit (data recorded in the 6-month baseline period) and the first follow-up visit. Efficacy variables were evaluated, including exacerbations, defined as the number of hospital admissions (mean and standard deviation [SD]), emergency department admissions (mean and SD), or the need for corticosteroid cycles (≥3 consecutive days). Exacerbations per patient refers to the number of exacerbation episodes during the baseline and follow-up periods. When more than one component occurred within the same clinical episode (e.g., emergency visits followed by hospitalization and/or OCS), the event was counted once as a single exacerbation episode, while emergency visits, hospital admissions, and OCS cycles were additionally reported as separate outcomes.

Procedure

Before starting the biological treatment, the patient's therapeutic adherence and correct inhalation technique were confirmed, an individualized educational plan was implemented, potential triggers or aggravating factors for exacerbations were identified, baseline treatment was adjusted, and associated comorbidities were evaluated.

Tezepelumab is indicated as add-on maintenance treatment in patients aged 12 years or older with severe asthma, inadequately controlled despite the use of high-dose ICS in conjunction with LABA and/or LAMA, who have had 2 or more exacerbations in the last year requiring treatment with OCS or systemic glucocorticoids or who have required hospitalization, according to GEMA 5.5 guidelines.

The index date was defined as the date of the first tezepelumab prescription. Baseline data were collected for the 6-month period prior to the index date, and outcomes were assessed at the first follow-up visit after initiation (approximately 6 months in routine practice).

We included all patients receiving tezepelumab for whom a comparative analysis could be performed between the 6-month baseline period (before starting tezepelumab) and the first follow-up visit. Therefore, patients without an available follow-up assessment were not included in the analytical cohort. Patients who had previously received another biologic without a satisfactory response were also included if they showed clinical criteria considered indicative of a lack of response to previous biological treatments, as follows: need for OCS after 12 months of biological treatment (prednisone > 5 mg/day), at least 1 severe exacerbation or hospitalization, and ACT score < 20 after at least 12 months of biological treatment. In patients requiring prednisone ≤5 mg/day for adrenal insufficiency, OCS use was considered unrelated to asthma.

Inflammatory phenotype was recorded in the e-CRF by the treating pulmonologist at each participating center according to GEMA 5.3 (version in force at the time of patient inclusion) guidance, based on clinical assessment and available biomarkers, and was subsequently extracted for the present analysis. T2 asthma was defined by the presence of any of the following: blood eosinophils ≥ 150 cells/μL; allergy (sensitization to aeroallergens, clinically relevant allergic disease and total immunoglobulin E ≥ 75 IU/mL); fractional exhaled nitric oxide ≥ 25 ppb; or sputum eosinophils > 3%.⁶ For subgroup analyses, allergic and eosinophilic phenotypes were grouped as T2, and all remaining patients were grouped as non-T2.

Clinical remission

Clinical remission at 6 months was defined as meeting REMAS-based clinical remission criteria at the first follow-up visit (approximately 6 months after initiation): controlled asthma (ACT ≥ 20), no OCS use, absence of exacerbations, and spirometry with FEV₁ ≥ 80%.⁷ Given the 6-month follow-up, remission was assessed at this time point and does not imply sustained remission over ≥12 months.

Statistical analysis

Patient data were extracted from electronic medical records stored on the MAMBRINO XXI® hospital information system. Quantitative variables are described using measures of central tendency (mean), along with their measure of dispersion (SD), depending on the variable. Qualitative variables are expressed as absolute and relative frequencies. For the differential analysis, the normal distribution of the sample was first evaluated in order to apply the corresponding parametric or non-parametric tests. Changes after tezepelumab treatment within the same patients (baseline vs follow-up) were assessed using the paired Student's t-test or the Wilcoxon signed-rank test, as appropriate. Paired dichotomous variables were analyzed using McNemar's test. Comparisons between independent groups (T2 vs non-T2; treatment-naïve vs non-naïve) were performed using the independent-samples Student's t-test or the Mann–Whitney U test for continuous variables, and the chi-square test for dichotomous variables. For key outcomes, 95% confidence intervals (CI) for the mean change from baseline were calculated based on the distribution of within-patient paired differences. Terms of interaction were explored in subgroup analyses to determine inter-group differences in the effect of tezepelumab. Statistical significance was defined as a 2-tailed p-value < 0.05. These statistical analyses were performed using IBM SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, USA).

Results

The study included a total of 48 patients diagnosed with severe asthma who received treatment with tezepelumab. All included patients had an available first follow-up assessment and no treatment discontinuations occurred prior to this visit. Mean patient age (SD) was 52.8 (14.8) years; most were women (70.8%), non-smokers (62.5%), overweight (mean body mass index [BMI] of 29.9 [6.8] kg/m²) and presented some comorbidity (91.7%). Most patients had a T2 phenotype (72.9%) and a previous history of monoclonal antibody treatment (56.3%). In terms of symptoms, patients showed poor asthma control with a mean ACT score of 12.8 (4.9). They had an obstructive ventilatory pattern with a mean FEV₁ of 1.99 (0.7) L, corresponding to 74.9 (22.2)%, and eosinophil levels of 190.9 (263) cells/μL; 14.5% were corticosteroid-dependent. In the 6 months prior to starting tezepelumab, the mean rate of exacerbations was 2.06 (1.9), and 80.4% of patients had had at least 1 exacerbation. Baseline patient characteristics are shown in Table 1.

Table 1.

Clinical and demographic characteristics of the study population.

Parameter	(n = 48)
Age, mean (SD), years	52.8 (14.8)
Sex, women, n (%)	34 (70.8)
BMI, mean (SD), kg/m^2	29.9 (6.8)
Smoking habit
Never smokers, n (%)	30 (62.5)
Former smokers, n (%)	18 (37.5)
Phenotype
T2, n (%)	35 (72.9)
Non-T2, n (%)	13 (27.1)
Comorbidities, n (%)	44 (91.7)
Nasal polyps, n (%)	10 (20.8)
Previous monoclonal antibody, n (%)	27 (56.3)
Benralizumab, n (%)	10 (20.9)
Dupilumab, n (%)	10 (20.9)
Mepolizumab, n (%)	5 (10.4)
Omalizumab, n (%)	2 (4.2)
ACT, mean (SD), score	12.8 (4.9)
FVC%, mean (SD), %	89.2 (22.2)
FVC, mean (SD), L	2.98 (0.8)
FEV1%, mean (SD), %	74.9 (22.2)
FEV1, mean (SD), L	1.99 (0.7)
FEV1/FVC, mean (SD), %	68.4 (14.9)
Eosinophils, mean (SD), cells/μL	190.9 (263)
Patients with exacerbations, n (%)	37 (80.4)
Exacerbations per patient, mean (SD)	2.06 (1.9)
Patients with chronic use of OCS, n (%)	7 (14.5)

Continuous variables are presented with mean (SD). Qualitative variables are shown as numerical counts.

ACT: asthma control test; BMI: body mass index; FEV₁: forced expiratory volume in 1 second; FEV₁%: percentage forced expiratory volume in 1 second; FVC: forced vital capacity; FVC%: percentage forced vital capacity; OCS: oral corticosteroids; SD: standard deviation; T2: inflammatory type 2 phenotype.

Clinical and functional variables were compared between the period prior to starting treatment (baseline) and the first follow-up visit (Table 2 and Fig. 1). At this visit (mean 6.25 [3.7] months after starting treatment), we observed a significant increase in the ACT score (+6.4 points, from 12.8 [4.9] to 19.2 [5.3]; p < 0.001), improved FEV₁ (+170 mL, from 1.99 [0.7] L to 2.16 [0.8] L; p = 0.01), and an 89% reduction in the mean number of exacerbations (from 2.06 [1.9] to 0.22 [0.46]; p < 0.001). We also found a decrease from 1.5 (1.4) to 0.2 (0.5) in OCS cycles, representing an 86% reduction (p < 0.001), and discontinuation of chronic OCS (from 7 patients [14.5%] to 2 [4.2%], a 71% reduction; p = 0.12).

Table 2.

Clinical and functional changes after treatment with tezepelumab.

N = 48	Baseline	Follow-up visit	Change from baseline (95% CI)	P value
ACT, mean (SD), score	12.8 (4.9)	19.2 (5.3)	6.4 (4.5, 7.5)	<0.001
FVC%, mean (SD), %	89.2 (22.2)	89.3 (18.4)	0.1 (–4.9, 6.9)	0.22
FVC, mean (SD), L	2.98 (0.8)	3.05 (0.9)	0.07 (–0.05, 0.19)	0.25
FEV1%, mean (SD), %	74.9 (22.2)	78.9 (21.3)	4 (–0.2, 8.0)	0.051
FEV1, mean (SD), L	1.99 (0.7)	2.16 (0.8)	0.17 (0.04, 0.28)	0.01
FEV1/FVC, mean (SD), %	68.4 (14.9)	69.7 (13.6)	1.3 (–2.3, 4.8)	0.48
Eosinophils, mean (SD), cells/μL	190.9 (263)	204.9 (215.8)	14 (–93.4, 97.4)	0.91
Exacerbations per patient, mean (SD)	2.06 (1.9)	0.22 (0.46)	–1.84 (–1.31, –2.39)	<0.001
OCS cycles, mean (SD)	1.5 (1.4)	0.2 (0.5)	–1.3 (–1.7, –0.9)	<0.001
Patients with chronic use of OCS, n (%)	7 (14.5)	2 (4.2)	–0.1 (–0.2, 0.01)	0.12
Emergency visits, mean (SD)	0.7 (1.3)	0.07 (0.3)	–0.6 (–0.9, –0.2)	0.001
Hospital admissions, mean (SD)	0.5 (1.1)	0.04 (0.2)	–0.5 (–0.7, –0.05)	<0.001

Continuous variables are presented with mean (SD). Qualitative variables were shown as absolute numbers.

ACT: asthma control test; CI: confidence interval; FEV₁: forced expiratory volume in 1 second; FEV₁%: percentage forced expiratory volume in 1 second; FVC: forced vital capacity; FVC%: percentage forced vital capacity; OCS: oral corticosteroids; SD: standard deviation.

Fig. 1.

Reduction in exacerbations in patients with severe asthma treated with tezepelumab. (a) Mean (%) of the number of patients who had exacerbations before starting tezepelumab and after the first follow-up visit; (b) Mean exacerbations per patient at baseline and at the follow-up visit.

The results were analyzed according to patients’ prior history of monoclonal antibody treatment. Treatment-naïve patients had worse baseline control (ACT: 11 [3.6] vs 14.2 [5.5]; p = 0.049), a higher rate of exacerbations (20 patients [95.2%] vs 17 patients [63%]; p = 0.03), and a higher number of OCS cycles (1.9 [1.4] vs 1.2 [1.4]; p < 0.03). No significant differences were observed in progress between the 2 groups, except for the reduction in OCS cycles, which was greater in the naïve group (–1.76 [1.4] vs –1 [1.2]; p < 0.04). These results are summarized in Table 3.

Table 3.

Clinical profile and progress according to previous monoclonal antibody treatment.

	Baseline			Difference follow-up visit vs baseline visit
	Treatment-naïve (n = 21)	Non-naïve (n = 27)	P value	Treatment-naïve (n = 21)	Non-naïve (n = 27)	P value
Age, mean (SD), years	52.9 (12.9)	52.8 (16.4)	0.9
Sex, women, n (%)	14 (66.7)	20 (74.1)	0.57
BMI, mean (SD), kg/m^2	31.6 (6.3)	28.6 (7.1)	0.58
Comorbidities, n (%)	20 (95.2)	24 (88.9)	0.62
ACT, mean (SD), score	11 (3.6)	14.2 (5.5)	0.04	6 (5.9)	6 (5.2)	1
FEV1, mean (SD), L	2.06 (0.7)	2.05 (0.9)	0.9	0.14 (0.4)	0.18 (0.4)	0.9
Eosinophils, mean (SD), cells/μL	175.3 (143.9)	202.6 (328)	0.7	–12.4 (183.9)	12.75 (376.5)	0.2
Patients with exacerbations, n (%)	20 (95.2)	17 (63)	0.03	3 (14.3)	6 (22.2)	0.7
Exacerbations per patient, mean (SD)	2.52 (1.8)	1.7 (1.9)	0.06	–2.3 (1.8)	–1.5 (1.8)	0.06
Patients with chronic use of OCS, n (%)	3 (14.3)	4 (14.8)	0.25	1 (4.8)	1 (3.7)	1
OCS cycles, mean (SD)	1.9 (1.4)	1.2 (1.4)	0.03	–1.76 (1.4)	–1 (1.2)	0.04

Continuous variables are presented with mean (SD). Qualitative variables are shown as numerical counts.

ACT: asthma control test; BMI: body mass index; FEV₁: forced expiratory volume in 1 second; OCS: oral corticosteroids; SD: standard deviation.

The results were also compared in terms of inflammatory phenotype (T2 vs non-T2). At the time of study inclusion, the non-T2 group had a higher BMI (28.5 [6.6] vs 34.4 [5.5]; p < 0.01), but no significant differences were observed among the other variables analyzed. After treatment, both groups showed clinical and functional improvement, along with a reduction in exacerbations and OCS use, although differences were not significant (Table 4).

Table 4.

Clinical profile and progress by inflammatory phenotype (T2 vs non-T2).

	Baseline			Difference follow-up visit vs baseline visit
	T2 (n = 35)	Non-T2 (n = 13)	P value	T2 (n = 35)	Non-T2 (n = 13)	P value
Age, mean (SD), years	51.1 (15.4)	57.7 (11.9)	0.2
Sex, women, n (%)	24 (68.6)	10 (76.9)	0.7
BMI, mean (SD), kg/m^2	28.5 (6.6)	34.4 (5.5)	<0.01
Comorbidities, n (%)	32 (91.4)	12 (92.3)	1
ACT, mean (SD), score	13 (5)	13 (5)	0.9	6.6 (5)	4.5 (5.6)	0.2
FEV1, mean (SD), L	2.13 (0.8)	1.83 (0.7)	0.2	0.20 (0.3)	0.05 (0.3)	0.2
Eosinophils, mean (SD), cells/μL	217 (296)	116 (110)	0.7	8.5 (354.2)	–16.4 (85.7)	0.8
Patients with exacerbations, n (%)	25 (71.4)	12 (92.3)	0.2	7 (20)	2 (15.4)	1
Exacerbations per patient, mean (SD)	2 (2)	2 (2)	0.4	–1.7 (1.8)	–2.23 (1.9)	0.4
Patients with chronic use of OCS, n (%)	4 (11.4)	3 (23.1)	0.4	2 (5.7)	0 (0)	1
OCS cycles, mean (SD)	1 (2)	2 (1)	0.2	–1.2 (1.4)	–1.6 (1)	0.2

Continuous variables are presented with mean (SD). Qualitative variables are shown as numerical counts.

ACT: asthma control test; BMI: body mass index; FEV₁: forced expiratory volume in 1 second; OCS: oral corticosteroids; SD: standard deviation; T2: inflammatory type 2 phenotype.

Finally, patient clinical remission, defined as ACT ≥ 20, absence of exacerbations, FEV₁ ≥ 80%, and OCS discontinuation, was evaluated at the first follow-up visit. One quarter (25%) of patients (n = 12) achieved remission according to these criteria.

Discussion

Real-world studies may differ from data obtained in pivotal clinical trials. This study confirms that the biologic drug tezepelumab reduces exacerbations and corticosteroid requirements and improves both lung function and asthma control, in line with the results of pivotal studies and other real-world series.

Our results were better in terms of reduced exacerbation rates than those observed in pivotal studies. While the PATHWAY⁴ and NAVIGATOR³ trials (both lasting 1 year) and the PASSAGE⁵ study (6 months) reported reductions versus placebo of 71%, 56% and 76%, respectively, the reduction reported in our cohort was 89% (from 2.06 to 0.22; p < 0.001). This reduction is higher than that reported by Khateeb et al. (12-month follow-up), in which the exacerbation rate decreased by 66.7% (from 2.88 to 0.96), and similar to that observed by Miralles et al. in a real-world study conducted in Murcia, Spain, where the exacerbation rate fell by 85.6% (from 2.63 to 0.38).^8,9 In line with these findings, a nationwide Danish real-world cohort also showed significant reductions in exacerbations at 12 months both in biologic-naïve patients (from 2.76 to 0.91) and in switchers (from 2.29 to 0.67).¹⁰ Furthermore, in the PATHWAY and NAVIGATOR studies, exacerbations requiring emergency care and/or hospitalization fell between 79% and 86% in the tezepelumab group compared to placebo. The PASSAGE study showed a 95% reduction in the rate of emergency visits among allergic patients and 77% among non-allergic patients, compared to 90% and 92% (0.7–0.07 and 0.5–0.04) in our cohort, respectively.

A notable characteristic of our cohort is the low number of corticosteroid-dependent patients. We have no conclusive explanation for this observation, but it could reflect a reluctance among our community to prescribe corticosteroids regularly due to their adverse effects. If they are prescribed, it is at the lowest effective dose and for the shortest possible time, and use is preferentially reserved for the last therapeutic step. The proportion of patients with severe OCS-dependent asthma at baseline who discontinued OCS treatment was numerically higher in the tezepelumab group than in the placebo group (37.9% vs 7.7% in NAVIGATOR³; 66.7% vs 46.9% in SOURCE¹¹). In our study, 71% of patients discontinued OCS (from 7 to 2 corticosteroid-dependent patients; p = 0.12). The number of OCS cycles also decreased significantly after treatment with tezepelumab (from 1.5 [1.4] to 0.2 [0.5]; p < 0.001). A real-world multicenter study recently conducted in more than 100 patients in Germany confirmed this sustained reduction in OCS use.¹²

With regard to lung function, a significant improvement in FEV₁ of 170 mL was observed, lower than that reported in NAVIGATOR³ (230 mL), but higher than that of PATHWAY⁴ (80 mL). FEV₁% increased numerically from 74.9% to 78.9%, but this change did not reach statistical significance (p = 0.051). The improvement in absolute FEV₁ is comparable to that reported in the Murcia cohort (188 mL) and the Khateeb cohort (210 mL).^8,9 Consistent with these findings, in the nationwide Danish cohort, many biologic-experienced patients (“switchers”) also experienced improvements in FEV₁ after 12 months of tezepelumab, with approximately one third of patients improving by more than 200 mL.¹⁰

Regarding asthma control, a 6.4-point increase was observed in the ACT score compared to baseline, more than double the 3-point threshold considered clinically significant, and higher than that reported in Murcia and Germany.^6,8

The results were also analyzed according to previous history of monoclonal antibody treatment and inflammatory phenotype (T2 vs. non-T2). Tezepelumab showed clinical benefits in patients previously treated with other biologics, including improved symptom control and lung function, as well as reduced exacerbations and use of OCS. These findings are consistent with other real-world series.^6,9,10 Patients with no previous history of biological treatment started tezepelumab with poorer symptom control, more exacerbations, and more OCS cycles. This group had a significantly greater reduction in OCS cycles compared to patients with previous history of biological treatment (–1.76 [1.4] vs –1 [1.2]; p < 0.04). Before starting treatment with tezepelumab, no significant differences were observed between the T2 and the non-T2 inflammatory phenotype groups, except for a higher BMI in the non-T2 group, and both groups showed better symptom control, increased lung function, fewer exacerbations, and reduced OCS use in the follow-up visit.

Finally, in the NAVIGATOR study,³ the proportion of patients who achieved a complete response (composite measure of absence of exacerbations, ACT > 20, FEV₁ > 80% and no OCS use) at 52 weeks was significantly higher in the tezepelumab group than in the placebo group (48.2% vs 25.3%; odds ratio 2.78; 95% confidence interval: 2.05–3.77). In our cohort, complete response was achieved in 25% of patients, a figure similar to that reported in the Murcia cohort (22.8%) and in the Khateeb cohort (23%).^8,9 In addition, real-world data from the nationwide Danish cohort suggest that clinical remission at 12 months may be more frequently achieved in biologic-naïve patients than in switchers (35% vs 15%, p = 0.01).¹⁰

Our study has limitations, such as the absence of a control group and the small sample sizes for subgroup analyses, which prevent us from drawing statistically significant conclusions for some variables. However, the results provide clinically significant information, as this is also one of the few studies addressing the impact of tezepelumab in a cohort of patients in the region of Castilla-La Mancha.

As more clinical experience is gathered and more studies are conducted, additional data may emerge on long-term efficacy, variability in patient response, and durability of remission.

This study, therefore, can be considered a valuable contribution to existing real-world evidence on the effects of tezepelumab in the management of uncontrolled asthma. In our series, the drug showed clinical benefits, with an 89% reduction in exacerbations, improved symptom control and lung function, and decreased use of OCS. A good response was observed in patients with or without previous biological treatment and regardless of inflammatory phenotype.

Conclusions

In this multicenter cohort of patients with severe uncontrolled asthma, treatment with tezepelumab was shown to be effective in real-world clinical practice, with a significant improvement in symptom control and lung function, and reduction in exacerbations and OCS use. These benefits were observed regardless of inflammatory phenotypes and previous treatment with other biologics, underlining the value of tezepelumab as a versatile therapeutic option in this patient profile.

Ethical considerations

The study complies with the basic ethical principles of non-maleficence, justice, autonomy, and beneficence and follows the ethical standards of the Declaration of Helsinki, adopted by the World Medical Association in June in 1964, and its subsequent amendments. Likewise, the privacy, confidentiality, and data protection of patients are guaranteed at all times.

Data protection is regulated in accordance with Regulation (EU) 2016/679 of the European Parliament and of the Council, dated 27 April 2016, on Data Protection, Organic Law 3/2018, dated 5 December, on Protection of Personal Data and Guarantee of Digital Rights, and Law 41/2002, dated 14 November, that governs patient autonomy. All study patients are included in the Severe Asthma Patient Registry of Castilla-La Mancha. The project was approved by the Ethics Committee for Research with Medicinal Products of Ciudad Real Integrated Care Management (C-419, April 2021), and all patients signed informed consent before inclusion.

Artificial intelligence involvement

During the preparation of this work the author(s) did not use generative AI or AI-assisted technologies in the writing or editing of the manuscript.

Informed consent

The study was approved by the Ethics Committee for Research with Medicinal Products of Ciudad Real Integrated Care Management (C-419, April 2021). Written informed consent was obtained from all participants prior to inclusion.

Funding

AstraZeneca funded the translation, adaptation, and submission of this manuscript to the journal but did not participate in the study design, conduct, analysis, content, or decision to publish.

Authors’ contributions

All authors have made substantial contributions to (1) the conception or design of the work, or the acquisition, analysis, or interpretation of data; (2) drafting the manuscript or revising it critically; (3) approval of the final version to be published.

Conflicts of interest

Carlos Bujalance-Cabrera, María José Espinosa de los Monteros-Garde, Diego Morena-Vallés, Raúl Godoy-Mayoral, Jesús Jiménez-López, Francisco Javier Lázaro-Polo, and José Luis Izquierdo-Alonso declare no conflict of interest. José Manuel Bravo-Nieto and Marta Jiménez-Arroyo report receiving payment or honoraria for lectures, presentations, manuscript writing, or educational events from AstraZeneca, GSK, and Sanofi, and support for attending meetings and/or travel from Sanofi.

Acknowledgments

The authors would like to thank Medical Statistics Consulting S.L. (Valencia, Spain) for their support in manuscript adaptation and translation, which was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).