¿p#1 Multidomain Clinical and Biological Remission with Tezepelumab in Severe Asthma: A 12-Month Multicentre Real-World Study

¿p#1 Background: Tezepelumab, an anti–thymic stromal lymphopoietin (TSLP) monoclonal antibody, has shown broad efficacy across severe asthma phenotypes. However, real-world evidence addressing multidomain remission, particularly with rigorous lung function criteria and detailed phenotypic characterisation, remains limited. Methods: This prospective multicentre study was conducted across 14 specialised asthma units in Spain. Clinical, functional, and biological parameters were assessed at baseline and after 12 months of tezepelumab treatment. Patients were classified as allergic, eosinophilic, or T2-low according to biomarker profiles. Clinical remission was defined as the absence of severe exacerbations, withdrawal of maintenance oral corticosteroids (OCS), an ACT score ≥20, and FEV 1 ≥80% predicted. Biological remission was defined as blood eosinophil count <300cell/mcL and fractional exhaled nitric oxide (FeNO) 5%) was also explored for comparison. Results: A total of 93 adults with severe asthma were analysed after 12 months of tezepelumab therapy. The annualised exacerbation rate decreased from 3.59 ± 2.45 to 1.14 ± 1.46 (−68%, p < 0.001). The greatest reduction in exacerbations was observed in the allergic phenotype (−78%), followed by eosinophilic (−72%) and T2-low (−65%). Maintenance OCS use dropped from 41% to 21% (p < 0.01), and mean ACT scores improved from 13.6 ± 4.9 to 19.8 ± 4.7 (p < 0.001). FEV 1 (% predicted) increased from 70.7 ± 23.5% to 75.6 ± 24.6% (p < 0.001), while FeNO and blood eosinophils significantly decreased (p = 0.034 and p = 0.004). Among evaluable patients (n = 77), 19 (22.1%) achieved strict clinical remission and 28 (36.4%) achieved pragmatic remission. Biological remission was reached in 73.1%, and complete remission in 22%. Conclusion: In this large multicentre real-world cohort, tezepelumab produced sustained improvements across clinical, functional, and inflammatory domains, with consistent benefit across allergic, eosinophilic, and T2-low phenotypes. By incorporating T2 biomarkers (FeNO and blood eosinophils) into the multidomain assessment of remission, this study provides new insight into the biological dimension of disease control. These findings support tezepelumab as a broad and durable treatment option capable of achieving clinically and biologically defined remission in severe asthma. ¿p#1 Introduction Severe asthma affects 5–10% of the asthma population and is associated with a disproportionate burden of exacerbations, impaired quality of life, and systemic corticosteroid (OCS) use (1, 2). Despite optimized treatment with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), many patients remain uncontrolled and require advanced therapies (3, 4). The introduction of monoclonal antibodies has transformed the management of severe asthma, particularly in type 2 (T2) inflammatory phenotypes (5, 6). Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, represents a novel upstream strategy that blocks multiple inflammatory pathways (7, 8). In pivotal randomized controlled trials (PATHWAY and NAVIGATOR), tezepelumab significantly reduced severe exacerbations, improved lung function, and enhanced asthma control across a broad range of patients, including those with low T2 biomarkers (9, 10). However, clinical trial populations often differ from those seen in real-world practice due to strict eligibility criteria and structured follow-up. Real-world studies have therefore become crucial to assess the external validity of trial findings and to explore outcomes such as OCS sparing and clinical remission in heterogeneous patient populations. Recent European and US cohorts have confirmed the effectiveness of tezepelumab in daily practice, but baseline severity and treatment patterns vary substantially across countries, influencing both utilization and outcomes (11-15). Clinical remission—defined as the absence of exacerbations, withdrawal of OCS, good symptom control, and preserved lung function—has recently emerged as a desirable treatment goal in severe asthma, reflecting a shift from disease control to disease modification. However, there is still no universal consensus on its definition, and the relative contribution of each clinical domain remains under debate (16-20). Real-world evidence on clinical remission with tezepelumab remains scarce, with only a few published studies reporting 12-month outcomes (13, 14). Building on this emerging evidence, we aimed to evaluate the long-term effectiveness and multidomain remission outcomes of tezepelumab in a real-world Spanish cohort. In this context, we conducted a prospective multicentre study with severe asthma patients treated with tezepelumab and followed for 12 months. The primary objective was to assess the effectiveness of tezepelumab and the proportion of patients achieving clinical and biological remission under routine clinical conditions. ¿p#1 Methods ¿p#1 Study design and setting This was a prospective, observational, multicentre real-world study conducted in 14 specialized severe asthma units across Spain. Consecutive adult patients (≥18 years) with severe asthma, as defined by GINA 2024 guideline (2), who initiated tezepelumab between October 2023 and October 2024 were included. Patients received tezepelumab 210 mg subcutaneously every 4 weeks according to routine clinical practice. Ethics The study was approved by the Clinical Research Ethics Committee of Cantabria (Spain) and subsequently acknowledged by all participating centres. All patients provided written informed consent prior to inclusion. The study was conducted in accordance with the Declaration of Helsinki and national regulations. ¿p#1 Data collection Data were collected at baseline (V1, treatment initiation) and at the 12-month follow-up visit (V2). Information was extracted from electronic medical records and structured clinical visits. A specific case report database (CRD) was designed for this study to ensure uniform data collection across all participating centres, using predefined variables and standardised definitions. Variables recorded included: • Demographics and clinical characteristics : age, sex, body mass index (BMI), smoking history, age at asthma onset, comorbidities (allergic rhinitis, chronic rhinosinusitis with nasal polyps [CRSwNP], bronchiectasis, COPD). • Asthma outcomes : number of severe exacerbations, hospital admissions, maintenance oral corticosteroid (mOCS), asthma control test (ACT) score, sinonasal outcome test (SNOT-22). • Treatment : maintenance OCS therapy, inhaled therapy (ICS/LABA, LAMA), leukotriene receptor antagonists, macrolides, prior biologics. • Lung function : FEV₁ (mL and % predicted), FVC (mL and % predicted). • Biomarkers : blood eosinophil count, total IgE, fractional exhaled nitric oxide (FeNO). FeNO was measured with standard devices (electrochemical or chemiluminescence analysers) according to ATS/ERS guidelines (21), using the same device per patient at baseline and follow-up. ¿p#1 Definitions Severe exacerbation : worsening of asthma requiring systemic corticosteroids ≥3 days, an emergency department visit, or hospitalization (2). Exacerbations separated by <7 days were considered a single event. Asthma phenotypes : Patients were classified according to type 2 (T2) inflammatory status and dominant clinical phenotype, as follows: • T2-high: defined by at least one of the following: blood eosinophils ≥150cell/mcL, FeNO ≥25 ppb, or evidence of allergic sensitisation with compatible clinical expression.Within the T2-high group, two distinct clinical phenotypes were identified: – Allergic phenotype: patients with positive allergen sensitisation tests and clinically relevant allergic symptoms upon exposure, regardless of blood eosinophil count.– Eosinophilic phenotype: patients with blood eosinophils ≥300cell/mcL, with or without positive allergen sensitisation, but in whom eosinophilic inflammation predominated over allergic symptoms.Patients fulfilling criteria for T2-high inflammation (eosinophils 150–299/μL and/or FeNO ≥25 ppb) but without clear allergic or eosinophilic predominance were classified as T2-high. • T2-low biomarkers: patients without any of the above features (blood eosinophils <150cell/mcL, FeNO <25 ppb, and no evidence of allergic sensitisation). • Clinical remission (strict definition) : no severe exacerbations, no maintenance OCS, ACT ≥20, and FEV₁ ≥80% predicted at 12 months after 1 year of treatment. • Clinical remission (pragmatic definition) : no severe exacerbations, no OCS, and ACT ≥20 and stable lung function, defined as a change in FEV1 not greater than 5% from the baseline measurement (decline ≤5%) after 1 year of treatment. • Biological remission : blood eosinophil count <300cell/mcL and FeNO <25 ppb after 1 year of treatment. • Complete remission : fulfilment of both clinical (strict) and biological remission criteria. ¿p#1 Statistical analysis Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]), depending on data distribution (assessed using the Shapiro–Wilk test). Categorical variables were summarised as counts and percentages. Comparisons between baseline and 12 months were performed using paired t-tests for normally distributed data or Wilcoxon signed-rank tests for non-normally distributed data. Student’s t-tests or Mann–Whitney U tests were used for comparisons between independent groups (e.g., patients with and without clinical remission). Categorical variables were compared using χ² tests or Fisher’s exact tests when expected cell counts were <5. Changes in paired binary outcomes (such as maintenance OCS use) were analysed with the McNemar test. The annualised exacerbation rate (AER) was analysed using negative binomial regression, adjusted for patient exposure time (12 months), and expressed as incidence rate ratios (IRR) with 95% confidence intervals (CI). Full IRR data are presented in Supplementary Table S1. Clinical remission was analysed in patients with complete baseline and 12-month data (complete-case analysis). To explore factors associated with achieving strict clinical remission, a multivariable logistic regression model was fitted, including the following baseline covariates: age, sex, body mass index (BMI), phenotype (T2-high vs. T2-low), biologic-naïve vs. switch, blood eosinophil count, and FeNO. Results are reported as odds ratios (OR) with 95% CI. Detailed model results are provided in Table 3. All statistical tests were two-sided, with p < 0.05 considered statistically significant. Analyses were conducted using R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria).

¿p#1 Patient population A total of 93 patients with severe asthma initiated tezepelumab and were included in the analysis and followed for 12 months. Seventy-seven patients had complete basal (V1) and 12 months (V2) paired data for the clinical remission composite score (16 patients with missing data) and fifty-two for the biological remission composite outcome. See flowchart showed as Figure S1. The mean age was 55.9 years, 71% were female, and the mean BMI was 30.4 kg/m². Fifty-five percent were biologic-naïve, while 44% had switched from another biologic. Regarding inflammatory phenotype, 62% were T2-high and 33% T2-low. At baseline, patients exhibited a high disease burden, with a mean annualized exacerbation rate (AER) of 3.59, 41% receiving maintenance oral corticosteroids (OCS), and 18% with chronic rhinosinusitis with nasal polyps (CRSwNP). See Table 1. Severe exacerbations The annualized exacerbation rate (AER) decreased from 3.59 ± 2.45 in the 12 months prior to initiation to 1.14 ± 1.46 at 12 months (−68%, p < 0.001) (Figure 1A). In a negative binomial model, the incidence rate ratio (IRR) for exacerbations at 1 year was 0.32 (95% CI 0.25–0.41, p < 0.001). Of those with at least one severe exacerbation in the previous year, 44.7% became exacerbation-free. Improvements were consistent across subgroups: biologic-naïve (IRR 0.27, 95% CI 0.18–0.39), biologic-switch (IRR 0.39, 95% CI 0.28–0.54). By phenotype, reductions were most pronounced in allergic asthma (IRR 0.22, 95% CI 0.14–0.36, p < 0.001) (Figure 1B) followed by eosinophilic (IRR 0.28, 95% CI 0.17–0.45) (Figure 1C), and T2-low asthma (IRR 0.35, 95% CI 0.24–0.52) (Figure 1D). Full incidence rate ratio data are provided in Supplementary Table S1. ¿p#1 Asthma control Asthma symptom control improved significantly, with ACT scores increasing from 13.6 ± 4.9 at baseline to 19.8 ± 4.7 at 12 months (p < 0.001). At 1 year, two-thirds of patients achieved good asthma control (ACT ≥20; Table 2). 65.8% of patients with uncontrolled symptoms at baseline (ACT < 20) achieved ACT ≥ 20 at 1 year. ¿p#1 Lung function FEV₁ (% predicted) improved significantly from 70.7% ± 23.5 at baseline to 75.6% ± 24.6 at 12 months (p < 0.001). Absolute FEV₁ increased numerically (1880 ± 807 mL to 1938 ± 845 mL; Δ +58 mL, ns) but this change did not reach statistical significance (p = 0.3) (Table 2). Only 17.5% of patients with impaired lung function (FEV₁ < 80%) improved to normal values (≥ 80%). ¿p#1 Oral corticosteroid use At baseline, 41% of patients were receiving maintenance OCS. After 12 months of treatment, this proportion decreased to 21% (p < 0.01) (Table 2). Among OCS-dependent patients, more than half discontinued systemic steroids during follow-up. 50% of those on maintenance OCS were able to discontinue systemic corticosteroids. ¿p#1 Biomarkers Blood eosinophil counts decreased from 211 ± 311 cells/µL at baseline to 125 ± 45 cells/µL at 1 year (p = 0.004). FeNO also declined significantly, from 24.4 ± 23.5 ppb to 18.9 ± 15.9 ppb (p = 0.034). Total IgE showed a nonsignificant downward trend (160 ± 241 IU/mL to 136 ± 185 IU/mL, p = 0.077) (Table 2). ¿p#1 Sinonasal outcomes In patients with CRSwNP, sinonasal symptoms improved substantially. Mean SNOT-22 scores decreased from 27.9 ± 18.5 at baseline to 16.3 ± 9.3 at 1 year (p < 0.001) (Table 2). ¿p#1 Remission outcome For the strict definition of clinical remission, data were available for 77 out of 93 patients (82.8%). Among these, 19 patients (22.1%) achieved clinical remission. When applying the pragmatic definition, data were available for the same 77 patients. Under this definition, 28 patients (36.4%) achieved clinical remission and 49 (63.6%) did not. The most frequently achieved domains were symptom control and OCS withdrawal, whereas lung function normalisation remained the most difficult. A summary of clinical remission outcomes is provided in Table 3. Biological remission was frequent, achieved by 73.1% of evaluable patients ( n = 38/52). As illustrated in Figure 2A, 22% of patients reached complete remission (both clinical and biological), 50% achieved biological remission without clinical remission, 2% achieved clinical remission without biological remission, and 26% did not meet either criterion. In Figure 2B, biological remission was more frequently observed in patients with higher baseline T2 biomarker levels—particularly those with FeNO ≥ 25 ppb and/or blood eosinophils ≥ 150 cells/μL—consistent with tezepelumab’s upstream mechanism of action and its strong anti-inflammatory effect across T2-driven endotypes. ¿p#1 Discussion In this multicentre real-world study including 93 patients with severe asthma, tezepelumab was associated with a substantial reduction in exacerbations, improvements in asthma control and lung function, decreased OCS dependence, and significant biomarker suppression after 12 months of follow-up. In addition, a relevant proportion of patients achieved clinical and biological remission, supporting the broad effectiveness of this upstream biologic in routine practice. ¿p#1 Exacerbations and oral corticosteroid use The reduction in exacerbations observed in our cohort (–68%) is consistent with the magnitude reported in other real-world studies. In the Israeli series of 103 patients, the AER decreased from 2.9 to 1.0, while in the UK cohort (n=175) the reduction was from 3.1 to 0.8. Similarly, the US PASSAGE study reported a decrease from 3.0 to 0.7. Our results therefore confirm the reproducibility of clinical trial data in real-world settings, despite differences in baseline severity. Importantly, we observed a halving of OCS dependence (from 41% to 21%), comparable to the OCS reduction described in Israel and the UK, and clinically relevant given the well-recognised long-term toxicity of systemic corticosteroids. ¿p#1 Symptom control and lung function Symptom control improved significantly, with two-thirds of patients achieving ACT ≥20. This rate is comparable to the proportion of patients with ACQ-6 <1.5 in the UK study (55%), confirming that tezepelumab translates into meaningful improvements in quality of life. Lung function also improved significantly in relative terms, although the absolute gain was modest, as reported in other real-world series. This reinforces the observation that lung function is often the most difficult domain to normalise in severe asthma. ¿p#1 Biomarkers and comorbidities Tezepelumab significantly reduced blood eosinophils and FeNO, consistent with its upstream anti-inflammatory action. Of note, sinonasal symptoms also improved, as shown by a marked decrease in SNOT-22 scores in patients with CRSwNP. This supports the dual impact of tezepelumab on both lower and upper airway inflammation and mirrors findings from post-hoc analyses of the NAVIGATOR trial. ¿p#1 Remission outcomes To our knowledge, this is the first multicentre real-world cohort to evaluate remission with tezepelumab using both a stringent lung function–based definition and the pragmatic approach applied in previous international cohorts. The remission analysis provides valuable insight into the multidimensional response to tezepelumab in routine care. Using the strict definition, clinical remission was achieved in 22.1% of evaluable patients, while 36.4% fulfilled the pragmatic definition. These results illustrate how remission rates vary depending on the stringency of lung function criteria and the heterogeneity of severe asthma populations in clinical practice. This finding is consistent with the recent systematic review and meta-analysis by Shackleford et al.(20), which reported a pooled clinical remission rate of 30% across studies using four-domain definitions. However, that analysis combined studies with heterogeneous FEV₁ criteria, ranging from stability thresholds to complete normalisation (FEV₁ ≥80% predicted), which likely contributed to the variability in remission estimates. By adopting the most rigorous criterion—FEV₁ ≥80% predicted—our study provides a conservative yet physiologically meaningful measure of remission, focusing on true functional normalisation rather than partial improvement. Our decision to use FEV₁ ≥ 80% as the core component of the strict remission definition is consistent with recent expert recommendations from Thawanaphong et al. (19) and the REMAS 2024 consensus (18), which highlight that lung function normalisation should be regarded as a marker of true disease modification rather than mere control, distinguishing patients who achieve partial improvement from those who experience near-complete recovery of airway function. Although this more demanding definition results in lower remission rates, it provides a rigorous benchmark to evaluate the full therapeutic potential of biologic agents. Consistent with previous studies, the domains most frequently achieved were symptom control and OCS withdrawal, whereas FEV₁ normalisation remained the most challenging.(13, 14, 22) The overlap between clinical and biological remission was partial: some patients achieved excellent symptom and exacerbation control despite persistent biomarker elevation, while others exhibited suppressed biomarkers without meeting full clinical remission criteria. This divergence suggests that tezepelumab may decouple symptomatic control from ongoing low-grade inflammation in certain patients—a phenomenon also observed in other real-world cohorts. Beyond the clinical domains, the suppression of type 2 (T2) inflammation was remarkable in our cohort, with 73.1% of evaluable patients achieving biological remission at 12 months. This finding confirms tezepelumab’s potent upstream anti-inflammatory action, as previously shown in the NAVIGATOR biomarker sub-analysis, where blood eosinophils and FeNO were reduced by approximately 50% and 25%, respectively, after 52 weeks of treatment (23). However, it is worth noting that all patients in NAVIGATOR were biologic-naïve, whereas in our real-world cohort only 54.8% were naïve and nearly half had been previously treated with anti–IL5/IL5R or anti–IL4R therapies—agents known to lower baseline biomarkers. As a result, baseline eosinophil counts (211 ± 311 cells/μL) and FeNO levels (24 ± 23 ppb) in our study were considerably lower than those reported in NAVIGATOR (approximately 300–350 cells/μL and 35–40 ppb). Similarly, Gates et al. reported consistent reductions in both parameters in a real-world population, though remission rates were not specifically quantified (13). Despite these lower starting levels, tezepelumab induced further suppression, leading to biomarker normalisation compatible with biological remission in nearly three quarters of evaluable patients. These effects were most evident in those with higher baseline T2 activity (FeNO ≥25 ppb and/or eosinophils ≥150/μL). The dissociation between biological and clinical remission observed in a subset of patients likely reflects the lag between inflammatory resolution and symptomatic recovery, as has been suggested in other longitudinal analyses. ¿p#1 Comparison with international cohorts Our findings align with and expand upon previous real-world experiences with tezepelumab. In the nationwide Danish cohort by Baastrup Soendergaard et al.(14) (n = 273), 63% of patients were switchers from another biologic, and treatment led to a 69% reduction in exacerbations, with significant improvements in ACT, AQLQ and FEV₁. Despite these benefits, strict clinical remission—defined identically to our criteria—was achieved in 35% of biologic-naïve patients and 15% of switchers, reflecting lower overall remission rates likely related to the higher proportion of heavily pretreated patients and lower baseline T2 biomarker levels. Similarly, the Israeli cohort (12) reported a 67% reduction in exacerbations, improvement in FEV₁ in over half of patients, and a 45% discontinuation rate of maintenance OCS, though remission outcomes were not assessed. In the UK cohort by Gates et al.(13), 36% of patients achieved clinical remission using a pragmatic definition, and 38% achieved biological remission. The US PASSAGE study confirmed comparable improvements in exacerbations, OCS use, and symptoms, albeit without remission data.(11) Taken together, these studies consistently demonstrate that tezepelumab provides broad, reproducible clinical benefits across diverse real-world settings. Importantly, the inclusion of multidomain remission assessment in our Spanish cohort distinguishes it from prior reports and underscores the potential of tezepelumab to achieve sustained disease control even in patients with high baseline severity. Our results not only confirm tezepelumab’s clinical effectiveness but also contribute to refining remission as a measurable, multidomain endpoint for severe asthma management in real-world settings. ¿p#1 Strengths and limitations The strengths of our study include its prospective multicentre design, the largest Spanish cohort reported to date, and a complete 1-year follow-up. The systematic evaluation of remission across multiple domains adds to the growing literature on this emerging treatment target. Limitations include the absence of a control group, potential unmeasured confounders inherent to observational studies, and inter-centre variability in FeNO measurement devices. The sample size, while larger than previous Spanish reports, still limits power for subgroup analyses. Missing data for FeNO (n = 13) and blood eosinophils (n = 35) at 12 months may have led to a conservative estimation of biological remission. ¿p#1 Clinical implications This 12-month, multicentre Spanish cohort provides robust real-world evidence on the effectiveness of tezepelumab across a wide spectrum of severe asthma phenotypes. The consistent reductions in exacerbations, OCS dependence, and type 2 inflammatory biomarkers confirm the broad anti-inflammatory potential of this upstream biologic, even in patients with high baseline disease burden and in T2-low phenotypes. Importantly, by jointly assessing clinical and biological remission, our study moves beyond conventional endpoints to capture both the symptomatic and inflammatory dimensions of disease control. The use of stringent and pragmatic definitions of clinical remission, together with the inclusion of biological remission based on T2 biomarkers (FeNO and eosinophils), provides a comprehensive picture of tezepelumab’s multidomain efficacy in real-world practice. These findings highlight the value of tezepelumab as a comprehensive and upstream treatment option capable of achieving deep remission in a subset of patients, while underscoring the challenge of reaching complete disease resolution. Future multicentre collaborations and long-term follow-up will be essential to confirm the durability of both clinical and biological remission and to consolidate remission as a realistic therapeutic endpoint in severe asthma. ¿p#1 Conclusions In this 12-month, multicentre, real-world study, tezepelumab demonstrated sustained effectiveness across clinical, functional, and biological domains, leading to marked reductions in exacerbations, OCS use, and type 2 inflammatory biomarkers, together with improvements in asthma control and lung function. By integrating both strict and pragmatic clinical remission criteria and incorporating biological remission into the multidomain evaluation, our study provides novel insight into the depth of response achievable with tezepelumab in severe asthma. The partial overlap between clinical and biological remission underscores the complex interplay between symptom control and inflammation resolution. Overall, these results confirm tezepelumab as a broad-spectrum, upstream biologic capable of inducing both clinical improvement and inflammatory quiescence across diverse phenotypes and disease severities in routine practice. ¿p#1 Author Contributions • Juan Luis García-Rivero: Conceived the study, led the data analysis, and drafted the manuscript. All authors contributed to data collection, critical manuscript revision, and approved the final version. • Miguel Santibáñez: Conceptualization, statistical analysis, manuscript drafting and critical revision. • Adil Hannaoui: Data curation, statistical analysis, and table preparation. • The remaining co-authors contributed to patient recruitment, data acquisition, and manuscript review. • *These authors contributed equally to this work Funding Statement: This study did not receive external funding. ¿p#1 Conflict of Interest: García-Rivero JL, reports speaker fees from Zambon, Gebro Pharma, Grifols, GSK, AstraZeneca, Chiesi, Menarini and Sanofi; consulting fees from GSK, AstraZeneca, ALK, and Sanofi; and research grants from AstraZeneca. Abel Pallarés-Sanmartín reports speaker fees from GSK, Sanofi, Gebro Pharma, AstraZeneca, Novartis, Teva, Chiesi and CIPLA, consulting fees from AstraZeneca, GSK and Sanofi. García-Hernáez R, reports speaker fees from Gebro Pharma, GSK, AstraZeneca, Menarini and Sanofi. Hermida Valverde T, reports speaker fees from GSK, AstraZeneca, Menarini and Sanofi; consulting fees from GSK, AstraZeneca and Sanofi. Garcia Gallardo Sanz MV, reports speaker fees from, Gebro Pharma, GSK, AstraZeneca, Chiesi, Menarini and Sanofi; consulting fees from GSK, AstraZeneca, and Sanofi. Dorronsoro Quintana, S, reports speaker fees from GSK, AstraZeneca and Menarini Calvo Álvarez U, reports speaker fees from GSK, AstraZeneca, Chiesi and Menarini. Carrascosa Anguiano, Ines reports speaker fees from GSK, AstraZeneca, Menarini, FAES, Orion and Sanofi; consulting fees from AstraZeneca, and research grants from AstraZeneca. Lobato Astiárraga I reports speaker fees from Gebro Pharma, GSK, AstraZeneca, Chiesi, and Sanofi. Enríquez Rodríguez AI, reports speaker fees from GSK, AstraZeneca, Menarini and Sanofi; consulting fees from GSK, AstraZeneca and Sanofi. Abascal-Bolado B, reports speaker fees from Gebro Pharma, GSK, AstraZeneca, Chiesi, Menarini and Sanofi. Santibañez M, reports speaker fees from GSK, Teva and Boehringer-Ingelheim. Perez-de-Llano L, reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from GSK, grants, personal fees and non-financial support from TEVA, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Sanofi, personal fees from MSD, personal fees from TECHDOW PHARMA, grants, personal fees and non-financial support from FAES, personal fees from Leo-Pharma, grants and personal fees from GEBRO, personal fees from GILEAD, outside the submitted work. All other authors declare no conflicts of interest related to this work. ¿p#1 Consent for Publication No individual patient data (including images, videos, or recordings) are included in this manuscript. Therefore, consent for publication was not required. All data presented were anonymized and analysed in aggregate form. Authors affirm that no identifiable personal information is contained within the article.

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Baseline characteristics of the study population according to clinical remission status after 12 months of tezepelumab treatment. Values are expressed as mean ± standard deviation (SD) or n (%). Comparisons between groups were performed using Student’s t-test or Mann–Whitney U test for continuous variables and χ² test or Fisher’s exact test for categorical variables, as appropriate. NS = not significant. T2-high: blood eosinophils ≥150cell/mcL and/or FeNO ≥20 ppb or evidence of allergic sensitization; T2-low: absence of these features. Biologic-naïve: patients without prior exposure to biologic therapy for severe asthma. CRSwNP: chronic rhinosinusitis with nasal polyps; OCS: oral corticosteroids; ICS: inhaled corticosteroids; LABA: long-acting β₂-agonist; LAMA: long-acting muscarinic antagonist. Table 2. Clinical, functional, and biomarker outcomes at baseline and after 12 months of tezepelumab treatment. ¿p#1 Values are expressed as mean ± standard deviation (SD) or n (%), as appropriate. Comparisons between baseline (V1) and 12 months (V3) were performed using paired t-tests for normally distributed variables or Wilcoxon signed-rank tests for non-normally distributed variables. For categorical outcomes, changes were assessed with McNemar’s test. ¿p#1 *Previous 12 months versus cumulative exacerbations during 12 months follow-up (mean + SD) ¶ Annualized severe exacerbations calculated as the total number of events per patient in the previous 12 months before treatment initiation. ¶¶ Twelve-month accumulated exacerbations following tezepelumab initiation. † SNOT-22 scores reported in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). †† Eosinophil granulocytes in peripheral blood count. OCS: oral corticosteroids; BD: bronchodilator; ACT: Asthma Control Test; FeNO: fractional exhaled nitric oxide; IgE: immunoglobulin E. Table 3. Predictors of clinical remission (strict definition) after 12 months of tezepelumab treatment. ¿p#1 Results from multivariable logistic regression including prespecified clinical and biological variables. Clinical remission was defined as the absence of severe exacerbations, no maintenance oral corticosteroid (OCS) use, ACT ≥ 20, and FEV₁ ≥ 80 % predicted at 12 months. Odds ratios (OR) are adjusted for all covariates shown. ¿p#1 Abbreviations: OR, odds ratio; CI, confidence interval; ACT, Asthma Control Test; FeNO, fractional exhaled nitric oxide; BMI, body mass index. ¿p#1 Figures Figure 1. Annualized exacerbation rate at baseline and after 12 months of tezepelumab treatment. Panels show the mean annualized severe exacerbation rate (AER) before treatment (baseline) and after 12 months of tezepelumab across the overall cohort and by asthma phenotype: (A) all patients, (B) allergic asthma, (C) eosinophilic asthma, and (D) T2-low asthma. Reductions were consistent across all groups, with the largest decrease observed in allergic patients (−78% overall; −87.8% in biologic-naïve; −64.5% in biologic-switch). Error bars represent standard deviation. p < 0.001 for all within-group comparisons. Figure 2. Clinical and biological remission after 12 months of tezepelumab treatment. (A) Overlap between clinical and biological remission. The panel shows the proportion of patients achieving clinical remission (rows) and biological remission (columns). Biological remission was defined as FeNO < 25 ppb and blood eosinophil count < 300 cells/μL. Complete remission (both clinical and biological) was achieved by 11 patients (22%), while 25 patients (50%) achieved biological remission without clinical remission, and 1 patient (2%) achieved clinical remission without biological remission. The remaining 13 patients (26%) did not meet either criterion. (B) Clinical remission rates according to baseline T2 biomarker profiles. Stacked bars represent the proportion of patients achieving clinical remission (red) or not (light). Categories correspond to combinations of baseline FeNO and blood eosinophil count (BEC) thresholds. Higher remission rates were observed in patients with elevated baseline biomarkers ( FeNO ≥ 25 ppb and/or BEC ≥ 150 cells/μL ) compared with those with low T2 biomarker levels. Information & Authors Information Version history Peer review timeline Published Respiratory Research Version of Record27 Feb 2026Published Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 235views 99downloads Citations Download citation Juan Luis García-Rivero, Abel Pallares-Sanmartin, Marina Blanco-Aparicio, et al. ¿p#1 Multidomain Clinical and Biological Remission with Tezepelumab in Severe Asthma: A 12-Month Multicentre Real-World Study. Authorea. 17 November 2025. DOI: https://doi.org/10.22541/au.176339535.59158541/v1 DOI: https://doi.org/10.22541/au.176339535.59158541/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.