Tezepelumab is a human monoclonal antibody directed against thymic stromal lymphopoietin that inhibits initiation of the type 2 inflammatory cascade. Several pivotal studies demonstrating tezepelumab effectiveness and leading to regulatory and marketing authorization have since been complemented by further evidence, most notably from the following studies: (a) for severe uncontrolled asthma, the PASSAGE phase 4 clinical trial, conducted in a routine clinical practice setting, found that tezepelumab significantly reduced exacerbations, including in underrepresented populations (African-Americans, adolescents, smokers, individuals with chronic obstructive pulmonary disease), and improved lung function, disease control, and quality of life. (b) For corticosteroid-dependent asthma, the WAYFINDER phase 3b clinical trial reported tezepelumab's effectiveness in reducing both dependency and the number of exacerbations as well as clinical remission in around a quarter of patients. (c) For chronic rhinosinusitis with nasal polyps, the WAYPOINT phase 3 clinical trial found that tezepelumab, after therapeutic optimization, decreased nasal polyp size and nasal congestion, improved clinical impact and sense of smell, and reduced the need for surgery. (d) For moderate-to-very severe chronic obstructive pulmonary disease, the COURSE phase 2a clinical trial reported a non-significant reduction in exacerbations, but also that reductions were greater for the type 2 phenotype (eosinophils ≥150cells/μL). In conclusion, up-to-date evidence confirms tezepelumab safety and efficacy in treating severe uncontrolled asthma in routine clinical practice and in managing corticosteroid-dependent asthma and chronic rhinosinusitis with nasal polyps.
Tezepelumab es un anticuerpo monoclonal humano dirigido frente a la linfopoyetina del estroma tímico, inhibiendo el inicio de la cascada inflamatoria tipo 2. Tras la publicación de los estudios pivotales que demostraron su eficacia y la posterior aprobación por las agencias reguladoras y su comercialización, diversos estudios han complementado la información disponible. Entre éstos destaca: a) en asma grave no controlada, el estudio PASSAGE de fase 4 (práctica clínica habitual) confirmó la reducción significativa de las exacerbaciones, incluso en poblaciones habitualmente infrarrepresentadas en los ensayos (afroamericanos, adolescentes, fumadores, EPOC), además de mejorar la función pulmonar, el control y la calidad de vida; b) en asma dependiente de la cortisona, el estudio WAYFINDER demostró la eficacia de tezepelumab en la reducción de cortisona y del número de exacerbaciones, además de conseguir que hasta un 23,4% alcanzase la remisión clínica; c) en rinosinusitis crónica con poliposis nasal, el ensayo clínico de fase 3 WAYPOINT, demostró que el tratamiento con tezepelumab disminuyó el tamaño de los pólipos nasales y la congestión nasal, además de mejorar el impacto clínico, el olfato y la necesidad de polipectomía; y d) en pacientes con la enfermedad pulmonar obstructiva crónica de moderada a muy grave, el ensayo clínico COURSE constató una reducción no significativa de las exacerbaciones, que resultó mayor en el subgrupo de pacientes con fenotipo T2 (eosinófilos ≥150células/μL). En conclusión, la nueva evidencia disponible de tezepelumab constata su eficacia y seguridad en asma grave en situación de práctica clínica habitual, en el asma dependiente de cortisona y en la rinosinusitis crónica con poliposis nasal.
Tezepelumab, a monoclonal antibody that blocks the epithelial alarmin called thymic stromal lymphopoietin (TSLP), inhibits initiation of the type 2 (T2) inflammatory cascade (whether originating from the innate or the acquired immune response) via type 2 innate lymphoid cells (ILC2) or type 2 helper T cells (Th2), respectively. It also possibly inhibits initiation of the non-T2 neutrophilic immune response via interleukin (IL)-17. Tezepelumab is indicated for the treatment of both the T2 and non-T2 severe uncontrolled asthma (SUA) phenotypes, with pivotal studies demonstrating its efficacy and safety for patients on medium-to-high doses of inhaled corticosteroids (ICS) and another controller and experiencing ≥2 exacerbations in the previous year. Tezepelumab significantly reduces exacerbations and bronchial hyperresponsiveness, and improves lung function, disease control, and quality of life (QoL).1–7 Consequently, the Global Initiative for Asthma (GINA)8 and the Spanish asthma guidelines (GEMA)9 both include this molecule among those recommended for SUA treatment, with the peculiarity, however, that it is currently the only molecule recommended for both the T2 and non-T2 phenotypes.
In 2023, prior to the drug's commercialization, a Barcelona Respiratory Network Foundation (BRN) asthma working group published a summary report of available evidence on tezepelumab and its possible positioning in clinical practice.10 Several studies have since supplemented the available evidence, particularly in relation to the treatment of SUA, corticosteroid (CS)-dependent asthma, chronic rhinosinusitis (CRS) with nasal polyps (NP), and chronic obstructive pulmonary disease (COPD). The objective of this report, which complements the above-mentioned BRN report, is to describe these new contributions.
Severe uncontrolled asthmaPhase 3 clinical trials of tezepelumab have included populations that are little representative of real-world patients. While, regardless of the inflammatory phenotype, it has been demonstrated that tezepelumab significantly reduces exacerbations and improves lung function and asthma control,1–3 those findings needed to be confirmed for real-life settings and for underrepresented populations.
Tezepelumab efficacy in routine clinical practice was confirmed by the 2025 interim analysis for PASSAGE,11 designed as a prospective, multicentre, open-label, phase 4 study. PASSAGE included US patients with SUA aged ≥12 years, with ≥2 exacerbations in the previous year, treated with medium-to-high doses of ICS and maintenance bronchodilators. The phenotypic classification combined blood eosinophil count (BEC) ≥300cells/μL and <300cells/μL with sensitization to aeroallergens. Exclusion criteria were minimal to facilitate the inclusion of a representative and heterogeneous cohort encompassing patient groups typically underrepresented in trials, namely, African-Americans, adolescents, ≥10 pack-year smokers/ex-smokers, and individuals with concomitant mild or moderate COPD. The approach adopted by PASSAGE responded to evidence that up to 90% of real-world patients with SUA would be ineligible for biologic trials.12,13
The interim analysis referred to 208 patients (two thirds female), with a mean age of 53 years, of whom 41% and 38% had BEC ≥300cells/μL and BEC <150cells/μL, respectively, and 56% had perennial allergen sensitization. The annualized asthma exacerbation rate (AAER) was 2.5, and typically underrepresented groups were adequately represented (17%, 5%, 23%, and 13% African-Americans, adolescents, smokers/ex-smokers, and individuals with mild-to-moderate COPD, respectively). After 12 months of treatment, the AAER fell by 76% (from 2.96 to 0.71 exacerbations per patient-year), and this fall, moreover, was consistent across phenotypes; reductions were 62% (95% confidence interval (CI): 43–74) and 79% (95% CI: 67–86) for non-allergic and allergic cases with BEC <300cells/μL, respectively, and were 82% (95% CI: 68–90) and 81% (95% CI: 67–89) for non-allergic and allergic cases with BEC ≥300cells/μL, respectively. As for patients with BEC <150cells/μL, the AAER fell by 64% (95% CI: 49–74) and by 77% (95% CI: 66–84) in patients showing evidence of clinically relevant perennial allergy.
Those findings reinforce tezepelumab's efficacy beyond the T2 profile. Also noteworthy was the fact that the typically underrepresented groups showed similar exacerbation reduction rates: 82% for African-Americans, 73% for adolescents, 71% for smokers/ex-smokers, and 66% for patients with concomitant COPD. Those results are especially relevant given the greater disease burden and healthcare inequities experienced by those population groups.14,15
Tezepelumab significantly improved lung function, asthma control, QoL, and CRS, and especially CRS with NP. For lung function at week 24, the mean increase in pre-bronchodilator forced expiratory volume in 1 second (FEV1) was 0.11L, rising to 0.19L for individuals with baseline FEV1 ≤80% predicted and to 0.28L in patients with BEC ≥300cells/μL and allergic status. As for asthma control and QoL, reductions of 1.1, 2.9, and 22.8 points were observed in the Asthma Control Questionnaire-6 (ACQ-6), Asthma Impairment and Risk Questionnaire (AIRQ), and Saint George Respiratory Questionnaire (SGRQ), respectively. Patients with CRS with NP especially showed significantly decreased Sinonasal Outcome Test-22 (SNOT-22) scores. Those improvements are consistent with an upstream mechanism of action that modulates broad inflammatory pathways beyond the T2 axis.16
Biomarker analyses showed reductions in BEC, total immunoglobulin E (IgE), and perennial allergen-specific IgE. Those findings, although not used to select candidates corresponding to the drug's indication, further support tezepelumab's broad anti-inflammatory activity. Regarding safety, the profile was consistent with previously documented controlled trial data, and the serious adverse event (AE) rate was low (7.7%).
While PASSAGE, as a single-arm study, has inherent limitations in terms of causal inference, its prospective, inclusive, multicentre design nonetheless adds significant value to the extant literature. Furthermore, the PASSAGE results are consistent with real-life findings for other biologics already used to treat asthma (mepolizumab, benralizumab, and dupilumab), which all produced significant reductions in exacerbations in pre–post designs.17–19 Overall, PASSAGE demonstrates that tezepelumab was associated with reduced exacerbations and improved lung function, clinical control, and QoL in a large and diverse population of patients with SUA. Its consistent efficacy across multiple phenotypes and clinical contexts reaffirms its role as a key therapeutic option for the management of patients with SUA.
Tezepelumab's impact on distal lung mechanics was highlighted in a recent study by Kupershmidt et al.20 of small airway dysfunction (SAD), which contributes to poor symptom control and exacerbations in SUA. SAD was evaluated in 34 patients using impulse oscillometry (IOS). The significant clinical effect of tezepelumab was evident in median baseline-to-6-month falls in frequency dependence of resistance (R5–R20) and the area of reactance (AX): from 0.16 to 0.08kPa/L/s (P<0.001) and from 1.62 to 0.80kPa/L (P<0.001), respectively. Substantial improvements were also achieved in spirometry values: FEV1 increased from 1.73 to 1.97L (P=0.001) and maximal mid-expiratory flow (MEF)25–75 increased from 1.26 to 1.73L/s (P=0.002). Most importantly, SAD prevalence dropped from 76% at baseline to 44% at follow-up (P=0.003). These physiological gains were closely associated with symptomatic improvement: patients with a ≥3 point increase in the Asthma Control Test (ACT) showed the greatest improvement in IOS parameters. The findings, which reinforce the role of SAD as a crucial ‘treatable trait’ in SUA, suggest that tezepelumab's upstream inhibition of TSLP restores small airway function, which correlates directly with better long-term asthma control.
Severe corticosteroid-dependent asthmaOral (i.e., systemic) corticosteroid (OCS) dependence remains a major challenge for the treatment of severe asthma. However, tezepelumab has been demonstrated to have the potential to significantly reduce prolonged exposure to OCS.
The SOURCE21 study, published in 2022, was the first phase 3 randomized, double-blind, placebo-controlled trial specifically designed to evaluate the OCS-sparing effect of tezepelumab. While no statistically significant differences between tezepelumab and placebo were observed in terms of a percentage reduction in patients on OCS at week 48 (i.e., the study did not meet its primary objective), clinically relevant reductions did occur: a 90%–100% reduction was observed in 54% and 46% of patients receiving tezepelumab and placebo, respectively. Those findings need to be interpreted in light of key methodological characteristics of the protocol, namely, an unusually prolonged reduction phase of 36 weeks, great flexibility in maintaining reduction attempts despite exacerbations and insufficient control, and an apparently phenotype-dependent response reflected in significant benefits for patients with BEC ≥150cells/μL.
The WAYFINDER22 study was specifically designed to overcome the methodological limitations of SOURCE and to confirm the OCS-sparing effect of tezepelumab for a larger cohort of OCS-dependent patients with SUA. This phase 3b, multicentre, open-label, single-arm trial included 298 adults with severe OCS-dependent asthma, treated with a stable prednisone or prednisolone dose of 5–40mg/day over 48 weeks. For WAYFINDER, unlike SOURCE, patients with inflammatory phenotypes were actively selected by preferentially including patients with current or previous eosinophilic inflammation (the goal was 80% of patients with BEC ≥150cells/μL). OCS tapering, based on a more structured and personalized protocol than used in previous studies, was adjusted according to objective endocrine parameters that ensured patient safety. It involved systematic proactive management of adrenal insufficiency based on measuring morning serum cortisol and performing, when necessary, adrenocorticotropic hormone (ACTH) stimulation tests. Patients with a preserved adrenal function had their OCS reduced to ≤5mg/day (the minimum physiological dose). Week 52 results confirmed tezepelumab efficacy as an OCS-sparing therapy that enabled large reductions in physiological levels: 89.9% of participants reduced their maintenance OCS to ≤5mg/day without loss of asthma control, and 50.3% completely discontinued maintenance OCS. Furthermore, efficacy was observed for all the analysed phenotypes, as defined by baseline BEC, fractional exhaled nitric oxide (FeNO), and allergy status, with the greatest effect observed for allergic and eosinophilic asthma with BEC ≥300cells/μL. A quarter of the patients (24.3%) achieved clinical remission – a figure which doubled for those starting with lower OCS doses (5–10mg/day) – and approximately two thirds experienced no exacerbations during the treatment period. An additional relevant finding was that 72% of the evaluated participants reaching maintenance OCS doses of 5mg/day had complete or partial adrenal insufficiency.
Evidence of the OCS-sparing effect of tezepelumab has been bolstered by long-term extension studies and real-world clinical practice data. In DESTINATION,7 an extension study for NAVIGATOR2,3 and SOURCE, more patients treated with tezepelumab vs placebo completely discontinued OCS by week 104 (57.3% vs 35.6%).7 Along the same lines, a study of 103 included patients conducted in a routine clinical practice setting by Khateeb et al.23 reported that almost half of the patients with SUA managed to completely discontinue OCS, and a further percentage reduced their dose by >50% – including both patients with low BEC values and previous exposure to another biologic. A similar German real-world study conducted by Biener et al.24 reported – despite the clinical and therapeutic heterogeneity of the included 129 patients – clinically relevant dose reductions that culminated in a median of ≤5mg/day after 6 months of follow-up.
The above data confirm that tezepelumab enables a significant and sustained reduction in OCS use by patients with SUA. The WAYFINDER study (compared to the SOURCE study) confirms the drug's effectiveness through a faster and more structured tapering protocol, and other real-life studies confirm similar results for different populations.22,23 However, while the observed reduction in OCS dose is clinically encouraging, WAYFINDER was designed as an open-label, single-arm trial without a placebo control group, so its results should ideally be confirmed with double-blind randomized controlled trials.
Chronic rhinosinusitis with nasal polypsThe upper airway performs essential gas exchange functions related to smell, phonation, and conditioning of inspired air.25 CRS with NP, an inflammatory disease with a significant clinical impact, is associated with symptoms that affect sleep and cause fatigue, namely, loss of smell, rhinorrhoea, nasal congestion, and facial pain.26
The main goal in treating CRS with NP is sustained inflammation control, reflected in smaller polyps, less need for OCS or surgery, and improved smell, QoL, and comorbidities.27 In 40%–50% of cases, CRS with NP is associated with asthma, usually T2 asthma.28–30 This association supports the unified airway hypothesis that, in both allergic and eosinophilic forms of asthma, pathophysiological mechanisms are shared by the upper and lower (bronchial) airways.31 The association with asthma influences management of CRS with NP, as it implies more severe disease and a greater recurrence risk after endoscopic sinus surgery.29,30
Treatment of CRS with NP, which depends on severity, impact on QoL, and refractoriness, includes intranasal washes, topical and systemic CS, ESS, and, more recently, biologics.26 Biologics targeting T2 inflammation – i.e., by blocking IgE, IL-5, IL-4, and IL-13 – have been shown to improve control, except for patients with elevated symptoms and insufficient response. A study demonstrating refractoriness and the need for new therapeutic targets reported that, 24 months after starting on biologics, 65.6%, 77.9%, and 7.1% of patients required OCS, antibiotics, and surgery, respectively, while 49.3% discontinued treatment.32
In Caucasian populations, T2 inflammation predominates (≈80%), whereas Th1/Th17 signatures, currently referred to as T1 and T3 endotypes, are more frequent in Asian populations.33,34 The complex and heterogeneous pathophysiology of CRS with NP is characterized by epithelial barrier dysfunction, alarmin imbalance, the activation of specific inflammatory pathways, and structural airway wall changes. Epithelial injury induces the release of alarmins that activate innate immune cells, modulating the function of antigen-presenting cells and initiating an inflammatory cascade in which TSLP is a key mediator.35 This axis integrates innate and adaptive responses within the T2 pathway. Studies of nasal tissue, furthermore, have shown elevated TSLP levels in patients with CRS with NP, comparatively to both patients with CRS without NP and healthy controls.36,37 Those findings position TSLP blockade as a key therapeutic target for CRS with NP.
In clinical development, tezepelumab has been shown to be effective in achieving key SUA treatment goals, namely, reduced exacerbation frequency, improved lung function and QoL, reduced need for oxygen therapy, and ameliorated asthma symptoms. In a post hoc analysis38 of NAVIGATOR2,3 results, the reduction in exacerbations after tezepelumab treatment was greater for more severe disease, i.e., in patients with CRS with NP who, at baseline, had more frequent exacerbations and higher T2 inflammation marker levels (circulating eosinophils and FeNO) than patients with CRS without NP. Furthermore, at 28 and 52 weeks, a significant improvement in SNOT-22-assessed nasal symptoms was observed in patients with a recent NP diagnosis and a history of NP. Recommended as the most suitable treatment for CRS with NP was a 210mg subcutaneous dose of tezepelumab administered every 4 weeks.
The phase 3 WAYPOINT39 trial evaluated 210mg of tezepelumab administered every 4 weeks for 52 weeks to adult patients with severe CRS with NP being treated with high doses of intranasal CS and with a history of OCS use in the previous year or of NP surgery 6–12 months previously. The main inclusion criteria were a Nasal Polyp Score (NPS) ≥5, a persistent Nasal Congestion Score (NCS) ≥2, and impaired QoL (SNOT-22 ≥30). The two main endpoints were patient-reported changes in the NCS and NPS at week 52, and secondary endpoints included patient-reported changes in smell loss, SNOT-22 and Lund-Mackay scores, time to NP surgery and/or to OCS administration, total symptom score, and University of Pennsylvania Smell Identification Test (UPSIT) score at week 52. By week 52, compared to placebo, tezepelumab significantly reduced the NPS by 2.08 points (95% CI: 2.4–1.76; P<0.001) and the NCS by 1.04 points (95% CI: 1.21–0.87; P<0.001). Noteworthy was the fact that this effect was produced very soon after the first tezepelumab dose: NPS and NCS improvement became evident at 4 and 2 weeks, respectively. Overall, tezepelumab was 7–9 times more likely than placebo to achieve a clinically relevant response. Furthermore, the NPS and NCS improvements were independent of sex, body mass index, previous sinonasal surgeries, and baseline BEC, while the strongest response was observed in patients with higher BEC values. In terms of adjusted mean differences between groups, tezepelumab significantly improved the SNOT-22 score by 27.44 (95% CI: 32.51–22.37) and the smell loss score by 1.01 (95% CI: 1.18–0.83). Furthermore, fewer patients on tezepelumab vs placebo required NP surgery (0.5% vs 22.0%; hazard ratio (HR)=0.02; 95% CI: 0.00–0.09) or OCS (5.2% vs 19.3%; HR=0.11; 95% CI: 0.04–0.25).
In conclusion, for patients with severe uncontrolled CRS with NP, tezepelumab produced a significant, rapid, and sustained improvement in NP and in symptoms, and this improvement was consistent across all nasal variables and across multiple patient subgroups. Furthermore, its favourable safety profile confirms tezepelumab as a robust therapeutic option in this clinical context.
Chronic obstructive pulmonary diseaseCOPD is a chronic, heterogeneous, and progressive respiratory disease characterized by persistent airflow limitation, chronic respiratory symptoms, and frequent exacerbations.40 The exacerbations increase hospitalization risk, accelerate lung deterioration, and negatively affect QoL. The fact that many patients, despite receiving triple inhaled therapy, i.e., ICS/long-acting beta-2 agonist (LABA)/long acting antimuscarinic antagonist (LAMA), continue to experience repeated exacerbations points to an unmet therapeutic need.41 For certain subgroups of COPD patients, biological therapies are effective,42–45 particularly when directed against T2 inflammatory pathways and when the BEC is high.
COURSE,46 a phase 2a, multicentre, double-blind, randomized, placebo-controlled trial, evaluated tezepelumab potential to treat patients with moderate-to-very severe COPD and a history of ≥2 exacerbations in the previous 12 months despite stable inhaled triple therapy. The primary objective was to determine whether tezepelumab, compared to placebo, could reduce the annualized rate of moderate/severe COPD exacerbations, and secondary objectives included, as well as safety and tolerability, the severe exacerbations rate, time to first exacerbation, lung function changes (pre-bronchodilator FEV1), and QoL changes measured using the SGRQ, COPD Assessment Test (CAT), and Evaluating Respiratory Symptoms (E-RS) instruments. Also analysed on an exploratory basis was the relationship between clinical response and biomarkers (eosinophils, FeNO, and blood neutrophils).
Included in COURSE were 333 ≥10 pack-year smokers/ex-smokers aged 40–80 years (165 on tezepelumab, 168 on placebo), with moderate-to-very severe COPD and ≥2 exacerbations in the previous 12 months. Baseline characteristics of the included patients were as follows: mean age 67 years; 68% ex-smokers and 32% current smokers; mean post-bronchodilator FEV1 of 41% predicted; mean SGRQ score 58 (highly impaired QoL); 41% BEC <150cells/μL, 42% BEC 150–299cells/μL, and 17% BEC ≥300cells/μL; and a low median FeNO of 15ppb. The sample was stratified by geographic region, number of previous exacerbations, and BEC value. Tezepelumab (420mg) or the placebo equivalent was administered subcutaneously every 4 weeks for 52 weeks.
Tezepelumab compared to placebo produced a non-significant AAER reduction (12%); P=0.41). The effect on exacerbations was more pronounced for higher BEC values: a reduction of 46% for BEC ≥300cells/μL compared to 37% for BEC ≥150cells/μL. No significant improvements were detected in pre-bronchodilator FEV1, nor were relevant differences observed in SGRQ and CAT scores. However, exploratory analyses pointed to modest improvements in other elevated inflammatory biomarkers. The fact that tezepelumab consistently reduced BEC and FeNO values confirmed the expected biological impact on airway inflammation. Safety profiles were similar for both groups: the most common AEs were respiratory infections, gastrointestinal disorders, and musculoskeletal disorders, and serious AEs occurred in comparable proportions in both groups.
The statistical power of the COURSE trial may have been affected by the COVID-19 pandemic reducing the overall frequency of exacerbations. Furthermore, the effect of tezepelumab in the total population may have been diluted by the inclusion of patients with low inflammatory levels (low BEC and FeNO). The COURSE findings overall would support the need for phase 3 trials with greater statistical power that select patients according to biomarkers. Although COURSE did not achieve its primary objective, it did highlight encouraging trends: a 17% reduction in moderate and severe exacerbations, a benefit for patients with BEC ≥150cells/μL (and especially BEC ≥300cells/μL), and modest improvements in lung function and QoL. The results suggest that BEC could be a key biomarker to predict response in selected subgroups of patients. Underway at the time of writing are 2 phase 3 studies designed to explore this possibility: EMBARK47 and JOURNEY.48
Tezepelumab safety, tolerability, and immunogenicityThe safety, tolerability, and immunogenicity of tezepelumab have been consistently demonstrated throughout its clinical development and in real-world settings. Below is a summary of these findings for the studies evaluated in this report:
NAVIGATOR2,3(pivotal trial). Tezepelumab demonstrated a safety profile comparable to placebo. The incidence of treatment-emergent anti-drug antibodies (ADAs) was low (around 5% of patients). Most ADAs were transient and of low titre, with no detectable impact on pharmacokinetics, clinical efficacy, or AE frequency.
PASSAGE11(phase 4 real-world study). Safety in a broad real-world population was consistent with controlled trials, with a low rate of serious AEs (7.7%). Immunogenicity monitoring in clinical practice confirmed that the development of ADAs remained infrequent and clinically insignificant in diverse populations.
WAYFINDER22(OCS-sparing study). Safety monitoring focused on managing potential adrenal insufficiency during OCS tapering. Immunogenicity findings were aligned with phase 3 results showing that ADAs did not interfere with tezepelumab's ability to reduce OCS dependence.
WAYPOINT39(CRS with NP). With a safety profile similar to placebo, tezepelumab was well-tolerated. The most frequent AEs (observed more for the placebo group as would be expected) were those already known for tezepelumab: upper respiratory tract infections, headache, epistaxis, worsened CRS with NP, and exacerbations. No anaphylactic reactions were reported, and the immunogenic profile was consistent with findings observed in the asthma programme.
COURSE46(COPD). Safety profiles were comparable between the treatment and placebo arms. The incidence of ADAs was low and similar to that observed for other indications, with no evidence that ADA development influenced safety or clinical outcomes in patients with COPD.
Recommendations for clinical practiceTezepelumab is indicated for patients with severe T2 and non-T2 uncontrolled asthma and recurrent exacerbations despite high-dose inhaled therapy. Safe OCS dose reduction should be gradual and closely monitored to prevent potential adrenal insufficiency, regardless of the significant OCS-sparing effect of the treatment. Small airway function should be systematically evaluated using IOS, particularly in symptomatic patients exhibiting high peripheral resistance (R5-R20) and area of reactance (AX) values. Patients should be formally assessed, using a multidimensional approach, between weeks 16 and 24, with success defined as a reduction of at least 50% in the annual exacerbation rate, a clinically meaningful improvement in ACT scores (≥3 points), and early gains in IOS parameters as sensitive markers of response.
ConclusionsUp-to-date evidence from recent trials and pivotal studies of tezepelumab confirm its safety profile (similar to that observed for placebo) and its efficacy in patients with SUA studied in real-world routine clinical practice settings (reduced exacerbations and improved lung function, clinical control, and QoL), in CS-dependent patients (reduced dependency, need for ≤5mg/day of OCS, and exacerbations), and in patients with CRS with NP after therapeutic optimization (reduced NP size, ameliorated nasal congestion, improved smell, and minimized need for surgery and for OCS). As for patients with moderate-to-very severe COPD (not selected by phenotype), tezepelumab produces a non-significant reduction in exacerbations overall, but produces a greater reduction in the subgroup with BEC ≥150cells/μL when considered in isolation. Finally, the low incidence of clinically relevant ADAs and the favourable safety profile observed across multiple indications – including CRS with NP and COPD – support long-term tezepelumab use with high clinical confidence, requiring only routine monitoring for common minor AEs such as nasopharyngitis and headache.
Declaration of generative AI and AI-assisted technologies in the writing processNo AI was used.
Informed consentThe manuscript is a revision of the topic, no patients were enrolled, informed consent was not necessary.
FundingThis report was commissioned by the Barcelona Respiratory Network (BRN).
Authors’ contributionsVP conceived the manuscript and designed the study. VP, PA, ACL, MME and IO wrote the manuscript and approved the submitted version.
Conflicts of interest- –
VP received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer-Ingelheim, Chiesi, Gebro, GSK, Luminova-Medwell, Sanofi and Trudell. Received help assistance to meeting travel from AstraZeneca, Chiesi and Sanofi. Act as a consultant for Chiesi and GSK.
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PA in the last three years, has received personal fees as a consultant or honoraria from GSK, Sanofi/Regeneron and AstraZeneca. The author has also received support for attendance at meetings and/or travel from GSK, Sanofi/Regeneron, AstraZeneca and Menarini. The author's institution has received grants or donations from GSK, Sanofi/Regeneron, AstraZeneca and Chiesi.
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ACL has received fees in the last 3 years for talks at meetings sponsored by AstraZeneca, Chiesi, GlaxoSmithKline, Gebro, MSD, Zambón, and Sanofi-Regeneron, has received travel and attendance expenses for conferences from Sanofi-Regeneron, GlaxoSmithKline, AstraZeneca, Chiesi, MSD, Gebro and has received funds/grants for research projects from several state agencies, non-profit foundations and AstraZeneca, Sanofi-Regeneron, GlaxoSmithKline and MSD.
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MME in the last three years received personal fees as a consultant or honoraria from Chiesi, GSK, Sanofi/Regeneron, AstraZeneca, Menarini, and Aldo-Union. The author has also received support for attendance at meetings and/or travel from Chiesi, GSK, Sanofi/Regeneron, AstraZeneca, Menarini, and Gebro. The author's institution has received grants or donations from GSK, Sanofi/Regeneron, and AstraZeneca.
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IO in the last three years received honoraria for speaking at sponsored meetings from AstraZeneca, Chiesi, GSK, Sanofi. Received help assistance to meeting travel from AstraZeneca, Chiesi and Sanofi. Act as a consultant for AstraZeneca, Chiesi, GSK.
