Christopher S. Ambrose

Purpose: Asthma affects 26 million individuals in the US, with severe cases driving high healthcare use and costs. Tezspire^TM (tezepelumab) has shown benefits in a Phase 4 real-world study, but real-world claims-based evidence is limited. This study evaluated the real-world effectiveness of tezepelumab by assessing changes in asthma exacerbations, healthcare use, and costs among persistent users. Methods: This retrospective cohort study used IQVIA’s PharMetrics Plus claims database linked with Prognos and Quest data (12/17/2020 – 5/31/2024). Patients aged ≥ 12 years with severe asthma were included if they had continuous 12-month pre- and post-index medical and pharmacy enrollment, and ≥ 10 tezepelumab claims during 12-month follow-up. The index date was the first tezepelumab claim. Outcomes were compared pre- and post-index and included annualized asthma exacerbation rate (AAER), exacerbation-related healthcare resource utilization (HCRU), and costs. Subgroup analyses were conducted by prior biologic use, blood eosinophil count (BEC), serum IgE, and comorbidities. Results: Among 337 patients (mean age: 50.8 years; 78.0% female), 44.8% were biologic-naive and 55.2% were biologic-experienced. AAER decreased by 49.1% (95% CI: 43.5% to 54.2%; p< 0.0001) following tezepelumab initiation, with greater reductions among biologic-naïve patients (55.7% [95% CI: 47.6% to 62.6%]; p< 0.0001) and those with high pre-tezepelumab BEC (87.1% [95% CI: 63.5% to 95.5%] for ≥ 300 cells/μL; p< 0.0001). Exacerbation-related healthcare use decreased, with mean inpatient, ED, and outpatient visits per patient declining from 0.14, 0.67, and 3.23 in the pre-index to 0.05, 0.37, and 1.63 in the post-index, respectively (p< 0.0001 for all). Associated mean costs per patient were reduced: inpatient from $2,171 to $551 (p=0.0003), ED from $755 to $356 (p=0.0002), and outpatient from $933 to $477 (p< 0.0001). Conclusion: Findings from this observational, retrospective analysis show substantial reductions in AAER, exacerbation-related HCRU and costs among patients treated with tezepelumab, with greater improvements observed among patients who were biologic-naive or with high BEC.

Purpose: Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods: This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV₁) or percent predicted peak expiratory flow rate (ppPEFR) ≥ 80%, and no long-term oral corticosteroid (LTOCS) use. Results: A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤ 0.001), no exacerbations (p< 0.001), well- or partly controlled asthma (p=0.047), a ppFEV₁ or ppPEFR ≥ 80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion: Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

Letter for the article Established and Emerging Biological Therapies for the Treatment of Comorbid Asthma and Chronic Obstructive Pulmonary Disease

There are limited recent data assessing all-cause mortality for US patients with severe asthma. This descriptive analysis evaluated all-cause mortality in a real-world cohort of US adults with subspecialist-treated severe asthma, examining patient characteristics among those who died, physician-reported primary causes of death, and associations with treatment class. CHRONICLE (NCT03373045) was an observational study of US adults (aged ≥18 years) with subspecialist-treated severe asthma, enrolled from February 2018 to October 2024. Patients met at least one of the following criteria: ongoing FDA-approved monoclonal antibody therapy, maintenance systemic corticosteroids (mSCS) for ≥50% of the prior year, or persistently uncontrolled asthma despite high-dosage inhaled corticosteroids and additional controllers. All-cause mortality was assessed descriptively, overall and by treatment class at time of death. Investigators reported primary causes of death and COVID-19 involvement. Treatment class exposure was calculated by the cumulative days on biologics and/or mSCS. Among 4366 enrolled patients, mean age was 54.7 years; 69.7% were female, 73.1% were White, and 18.6% were Black. Over 14,758 person-years of observation, 130 deaths occurred (3.0%), yielding a mortality of 8.8 (95% confidence interval: 7.4, 10.5) per 1000 person-years. Cardiovascular disease was the leading cause of death (25.4%), followed by cancer (13.1%) and asthma (1.5%). COVID-19 contributed to 8.5% of deaths. Observed associations for all-cause mortality ranged from 6.8 per 1000 person-years in patients who were receiving biologics without mSCS to 31.6 per 1000 person-years in those receiving mSCS without biologics. US adults with subspecialist-treated severe asthma have an increased risk of all-cause mortality, especially those patients receiving mSCS. These findings highlight the importance of identifying mortality risks and limiting the use of mSCS whenever possible while supporting further research into the relationship between severe asthma and cardiovascular disease.

A subset of patients with severe asthma (SA) has normal lung function, defined by a pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) of

Background: Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health‐related quality of life and posing a safety hazard. Methods: WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 weeks. Results: Among 408 patients (tezepelumab [ n = 203]; placebo [ n = 205]), significant improvements with tezepelumab versus placebo in NPSD loss of smell item, UPSIT, and SNOT‐22 loss of smell/taste item scores were seen at week 4 (least‐squares mean [LSM] treatment difference [95% CI]: −0.36 [−0.46, −0.27]; 6.03 [4.72, 7.34]; and −1.01 [−1.22, −0.80], respectively) and week 52 (−1.01 [−1.18, −0.83]; 9.50 [7.84, 11.16]; and −1.90 [−2.20, −1.61]); all nominal p  < 0.0001. Between‐treatment differences in daily NPSD loss of smell item score were evident from day 7 (LSM treatment difference: −0.08 [95% CI: −0.15, −0.02]; nominal p  < 0.01). Improvements in NPSD loss of smell, UPSIT, and SNOT‐22 loss of smell/taste item scores were observed across multiple prespecified subgroups. Anosmia prevalence was lower with tezepelumab than placebo at week 4 (43.0% [ n/N = 64/149] vs. 80.3% [ n/N = 106/132]) and week 52 (31.5% [ n/N = 47/149] vs. 75.8% [ n/N = 100/132]). Conclusions: Tezepelumab provides early and sustained improvements in sense of smell among patients with uncontrolled CRSwNP.