Annualized Asthma Exacerbation Rate Research Articles

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study.

Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR. NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210mg or placebo subcutaneously every 4weeks for 52weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study. Tezepelumab reduced the AAER over 52weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline. These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers' treatment decisions. NAVIGATOR (NCT03347279).

Multivariate Cluster Analyses to Characterize Asthma Heterogeneity and Benralizumab Responsiveness

An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions. Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach. In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to simultaneously analyze 11 clinical characteristics. Annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters. Patients (N = 2,281) met criteria for 4 of 5 clusters: Cluster 2 (early-onset moderate asthma, n = 393), Cluster 4 (early-onset severe, n = 386), Cluster 3 (late-onset severe, n = 641), and Cluster 5 (late-onset severe, obstructed, n = 861); no patients met Cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe (-48% [95% CI: -61%, -31%], P<.0001) and late-onset severe, obstructed asthma (-50% [95% CI: -59%, -38%], P<.0001), with non-significant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Forced expiratory volume in 1 second improvements were significant in late-onset severe (+133 mL [95% CI: 66 mL, 200 mL], P=.0001) and late-onset severe, obstructed asthma (+160 mL [95% CI: 85 mL, 235 mL], P<.0001) while maintaining acute bronchodilator responsiveness. Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches.

Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia

BackgroundBenralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. ObjectiveTo evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. MethodsMIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12–75 years with severe asthma receiving medium- to high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1 is being defined, not BD, which has already been defined) and total asthma symptom score (TASS). Safety was evaluated ≤Week 56. ResultsOf 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p <0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p <0.0001) and TASS (LSD −0.25 [−0.45, −0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. ConclusionsMIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Tezepelumab in patients with allergic and eosinophilic asthma.

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.

Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review.

Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.

Tezepelumab reduces exacerbations across all seasons in patients with severe, uncontrolled asthma (NAVIGATOR)

BackgroundAsthma exacerbation frequencies vary throughout the year owing to seasonal triggers. Tezepelumab is a human monoclonal antibody that targets thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) vs placebo in patients with severe, uncontrolled asthma. ObjectiveTo evaluate the effect of tezepelumab on asthma exacerbations across all seasons in NAVIGATOR patients (post hoc). MethodsNAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. AAER over 52 weeks was assessed by season. Data from patients in the Southern Hemisphere were transformed to align with Northern Hemisphere seasons. ResultsTezepelumab reduced the AAER vs placebo by 63% (95% confidence interval [CI], 52-72) in winter, 46% (95% CI, 26-61) in spring, 62% (95% CI, 48-73) in summer, and 54% (95% CI, 41-64) in fall. In matched climates, during the spring allergy season (March 1 to June 15) and ragweed allergy season (September), tezepelumab reduced the AAER vs placebo in patients with seasonal allergy by 59% (95% CI, 29-77) and 70% (95% CI, 33-87), respectively. In patients with perennial allergy and in those with seasonal allergy, tezepelumab reduced the AAER vs placebo across all seasons. ConclusionTezepelumab reduced exacerbations across all seasons vs placebo in patients with severe, uncontrolled asthma, including patients with seasonal and perennial allergies. These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma. Trial RegistrationClinicalTrials.gov Identifier: NCT03347279 (https://clinicaltrials.gov/ct2/show/NCT03347279)

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study

BackgroundAsthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds).MethodsThe Clinical Practice Research Datalink Aurum...

Effects of Tezepelumab on Quality of Life of Patients with Moderate-to-Severe, Uncontrolled Asthma: Systematic Review and Meta-Analysis.

To assess the effects of tezepelumab on quality of life (QoL) in patients with moderate-to-severe, uncontrolled asthma. Tezepelumab improves pulmonary function tests (PFTs) and reduces the annualized asthma exacerbation rate (AAER) in patients with moderate-to-severe, uncontrolled asthma. We searched MEDLINE, Embase, and Cochrane Library from inception to September 2022. We included randomized controlled trials comparing tezepelumab versus placebo in patients aged ≥ 12years with asthma on medium- or high-dose inhaled corticosteroids with ≥ 1 additional controller medication for ≥ 6months and who had ≥ 1 asthma exacerbation in the 12months before enrollment. We estimated effects measures with a random-effects model. Of 239 records identified, three studies were included, with a total of 1,484 patients. Tezepelumab significantly decreased biomarkers of T helper 2-driven inflammation, including blood eosinophil count (MD -135.8 [95% CI -164.37, -107.23]) and fractional exhaled nitric oxide (MD -9.64 [95% CI -13.75, -5.53]); improved PFTs, including pre-bronchodilator forced expiratory volume in 1s (MD 0.18 [95% CI 0.08-0.27]); reduced the AAER (MD 0.47 [95% CI 0.39-0.56]); improved asthma-specific health-related QoL in the Asthma Control Questionnaire-6 (MD -0.33 [95% CI -0.34, -0.32]), Asthma Quality of Life Questionnaire for 12 Years and Older (MD 0.34 [95% CI 0.33, -0.35]), Asthma Symptom Diary (MD -0.11 [95% CI -0.18, -0.04]), and European Quality of Life 5 Dimensions 5 Levels Questionnaire (SMD 3.29 [95% CI 2.03, 4.55]) scores, although not clinically important; and did not change key safety outcomes, including any adverse event (OR 0.78 [95% CI 0.56-1.09]).

Tezepelumab Reduces Exacerbations Across All Seasons In Patients With Severe, Uncontrolled Asthma With Seasonal Allergy: Results From The Phase 3 NAVIGATOR Study

Exposure to seasonal allergens may contribute to spatiotemporal variations in asthma exacerbations. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab, reduced the annualized asthma exacerbation rate (AAER) versus placebo in patients with severe, uncontrolled asthma, across all seasons. This post hoc analysis evaluated the effect of tezepelumab on seasonal asthma exacerbations.

Allergology: what's new in 2022

The study of reactions to SARS-CoV-2 vaccines has marked a large part of the literature in the last two years, using the basophil activation test (BAT) as a potential diagnostic tool for reactions to Covid-19 vaccines. In allergic rhinoconjunctivitis, lirentelimab (a humanised monoclonal antibody against lectin 8), reduces patients' symptoms and atopic comorbidities. In severe asthma, tezepelumab (human monoclonal antibody) reduces the annual asthma exacerbation rate over 52 weeks. In terms of diet, the new EAACI guidelines recommend avoiding cow's milk supplementation in infants during the first three days of life to reduce the risk of cow's milk allergy.

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA AND HIGH BASELINE BLOOD EOSINOPHIL COUNTS

<h3>Introduction</h3> The efficacy of biologics for severe asthma is greater in patients with higher blood eosinophil counts (BECs) than those with lower BECs. Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma, irrespective of baseline BECs. This exploratory analysis assessed the efficacy of tezepelumab in patients with high baseline BECs (≥ 500 cells/μL) in NAVIGATOR. <h3>Methods</h3> NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. At week 52, AAER and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) were assessed by baseline BEC (≥ 500, ≥ 750 and ≥ 1000 cells/μL). <h3>Results</h3> Of 1059 patients, 209 had BECs ≥ 500 cells/μL, 76 had BECs ≥ 750 cells/μL and 33 had BECs ≥ 1000 cells/μL at baseline. Among placebo recipients, AAERs increased with increasing BEC. Tezepelumab reduced the AAER versus placebo by 74–77% across these BEC subgroups (<b>Figure</b>). Tezepelumab improved pre-BD FEV₁: least squares mean differences versus placebo were 0.26 L (95% confidence interval [CI]: 0.15–0.37), 0.21 L (95% CI: 0.02–0.40) and 0.41 L (95% CI: 0.13–0.69) in patients with baseline BECs ≥ 500, ≥ 750 and ≥ 1000 cells/μL, respectively. <h3>Conclusion</h3> Tezepelumab substantially reduced exacerbations and improved lung function versus placebo in patients with severe, uncontrolled asthma across all subgroups with high baseline BECs.

EFFICACY OF BIOLOGICS IN PATIENTS WITH SEVERE ALLERGIC ASTHMA, OVERALL AND BY BLOOD EOSINOPHIL COUNT

<h3>Introduction</h3> Patients with uncontrolled, severe allergic asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). Here we describe annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with severe allergic asthma overall and by baseline BEC category. <h3>Methods</h3> A literature search was performed to identify published phase 3 RCT data of FDA-approved biologics in patients with severe, uncontrolled asthma with confirmed allergy to perennial aeroallergens, where AAER reduction versus placebo was measured in the overall population and/or in those with a high or low BEC at baseline or screening. <h3>Results</h3> The serum total immunoglobulin E levels varied between biologic RCT analyses. In the overall allergic population, data were available for tezepelumab, dupilumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergy and BECs of at least 260 cells/μL or at least 300 cells/μL or higher, AAER reductions were observed with all biologics; the smallest AAER reduction was observed with omalizumab. In patients with allergy and BEC less than 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with mepolizumab, benralizumab or omalizumab. (<b>Figure</b>). <h3>Conclusion</h3> Among patients with severe allergic asthma, tezepelumab was the only biologic to demonstrate reductions consistently in AAER across all subgroups. The efficacy of biologics varies considerably overall and by BEC. These differences can inform provider treatment decisions.

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH UNCONTROLLED ASTHMA DESPITE RECEIVING TREATMENT FOR MODERATE OR SEVERE DISEASE: POOLED ANALYSIS OF PATHWAY AND NAVIGATOR STUDIES

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH UNCONTROLLED ASTHMA DESPITE RECEIVING TREATMENT FOR MODERATE OR SEVERE DISEASE: POOLED ANALYSIS OF PATHWAY AND NAVIGATOR STUDIES

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA BY SMOKING HISTORY: POST HOC ANALYSIS OF THE PHASE 3 NAVIGATOR STUDY

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA BY SMOKING HISTORY: POST HOC ANALYSIS OF THE PHASE 3 NAVIGATOR STUDY

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA GROUPED BY NUMBER OF ADDITIONAL ASTHMA CONTROLLER MEDICATIONS: RESULTS FROM THE PHASE 3 NAVIGATOR STUDY

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA GROUPED BY NUMBER OF ADDITIONAL ASTHMA CONTROLLER MEDICATIONS: RESULTS FROM THE PHASE 3 NAVIGATOR STUDY

PASSAGE: A PHASE 4, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF TEZEPELUMAB IN PATIENTS WITH SEVERE ASTHMA, INCLUDING UNDER-REPRESENTED GROUPS

PASSAGE: A PHASE 4, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF TEZEPELUMAB IN PATIENTS WITH SEVERE ASTHMA, INCLUDING UNDER-REPRESENTED GROUPS

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

BackgroundMany severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.MethodsBaseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.ResultsBetween January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).ConclusionAround one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Efficacy and safety of tezepelumab in patients recruited in Japan who participated in the phase 3 NAVIGATOR study

BackgroundTezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan. MethodsNAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed. ResultsOverall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV1 was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was −1.12 (0.15) and −0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%). ConclusionsTezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study

Objective To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma. Methods This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12–80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity. Results Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52). Conclusion Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.