Real-World Impact of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Italy: A Retrospective Study from a Cystic Fibrosis Center.

Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF. This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months. The study included 2645 pwCF from 67 centres in Germany (mean age 28.0±11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p<0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p<0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4kg/m2 (95% CI 1.3-1.4, p<0.0001), pulmonary exacerbations decreased by 75.9% (p<0.0001) and mean sweat chloride concentration decreased by 50.9mmol/L (95% CI -52.6,-49.3, p<0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment. These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele. None.

Early Aggressive Intervention in Cystic Fibrosis: Is It Time To Redefine Our “Best Practice” Strategies?

Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment

Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12years in the US. We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

PND80 - AN OBSERVATIONAL STUDY OF IVACAFTOR IN PATIENTS WITH CYSTIC FIBROSIS IN FRANCE: FIRST INTERIM ANALYSIS OF HEALTH CARE RESOURCE UTILIZATION FROM THE BRIO STUDY

Real-world effectiveness of benralizumab: Results from the ZEPHYR 1 Study

The utility of the forced oscillation technique in assessing bronchodilator responsiveness in patients with asthma

Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral-associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1s (FEV1 ) after an appropriate treatment. We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudinally evaluated three times: at baseline (Visit 1), at the diagnosis of pulmonary exacerbation (Visit 2), and after exacerbation treatment (Visit 3). Nasal and bronchial samples were analyzed at each visit with multiplex viral respiratory PCR panel (qualitative detection of 16 viruses). Pulmonary function tests were recorded at each visit, in order to highlight a possible failure to improve them after treatment. Lack of improvement was defined by an increase in FEV1 less than 5% between Visit 2 and Visit 3. Eighteen children were analyzed in the study. 10 patients failed to improve by more than 5% their FEV1 between Visit 2 and Visit 3. Rhinovirus infection at Visit 2 or Visit 3 was the only risk factor significantly associated with such a failure (OR, 12; 95% CI, 1·3-111·3), P=0·03. Rhinovirus infection seems to play a role in the FEV1 recovery after pulmonary exacerbation treatment in children with cystic fibrosis. Such an association needs to be confirmed by a large-scale study because this finding may have important implications for pulmonary exacerbation management.

Treatment of COPD: Relationships between daily dosing frequency, adherence, resource use, and costs

Malnutrition in children with cystic fibrosis: the energy-balance equation.

Dornase Alfa Therapy in Cystic Fibrosis: Who Should Get It?

Introduction: Seminal clinical trials with the triple combination of elexacaftor-tezacaftor-ivacaftor (ETI) demonstrated clinical efficacy in people with cystic fibrosis (pwCF) who carry at least one F508del mutation. However, due to exclusion criteria of these clinical trials, the effect of ETI was not studied in a substantial number of pwCF. Thus, we ran a single center trial to evaluate a clinical efficacy of ETI treatment in adult pwCF who were ineligible for enrollment in registration studies. Methods: PwCF on ETI with prior lumacaftor-ivacaftor therapy, severe airway obstruction, well-preserved lung function, or with airway infection with pathogens at risk of more rapid decline in lung function formed the study group, while all the others on ETI formed the control group. Lung function, nutritional status and sweat chloride concentration were assessed before and after initialization of ETI therapy over a 6-month period. Results: Approximately a half of the ETI-treated pwCF at the adult Prague CF center (49 of 96) were assigned to the study group. Their mean changes in body mass index ( + 1.04kg/m2) and in sweat chloride concentration (-48.4mmol/L) were similar to the control group ( + 1.02kg/m2; -49.7mmol/L), while the mean change in percent predicted forced expiratory volume in 1s (ppFEV1; + 10.3 points) was significantly lower than in the control group ( + 15.8 points) (p = 0.0015). In the subgroup analysis, pwCF with severe airway obstruction (ppFEV1 <40) and pwCF with well-preserved lung function (ppFEV1 >90) showed a less potential for improvement in lung function during the ETI treatment than controls (median change in ppFEV1 + 4.9 points and + 9.5 points, respectively). Conclusion: PwCF not eligible for inclusion in clinical trials demonstrated improvement in lung function and nutritional status following the initiation of treatment with the ETI combination. Moderate increase in ppFEV1 was observed in those with severe airway obstruction or well-preserved lung function.

A new diagnosis of chronic obstructive pulmonary disease (COPD) is often made during the evaluation of patients requiring a surgical intervention for lung cancer. Based on initial impaired lung function, these untreated patients are often considered not fit for lung surgery. There is limited information on the short-term effectiveness of preoperative pharmacologic treatment strategies in patients with newly diagnosed COPD before lung surgery. A prospective randomized study was conducted comparing 1-week-treatment periods of tiotropium/formoterol/budenoside (GR1) with tiotropium/formoterol (GR2) in conjunction with smoking cessation and chest physiotherapy. No patients had been previously treated for COPD. The primary end point was body plethysmography (forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and airway resistance (RAW)) at the end of each treatment period. Secondary end points were improvement of ≥ 10% in FEV1 (% predicted) and improvement of the severity of COPD after the 1-week treatment, as well as the rate of pulmonary complications after surgery. A total of 46 patients were randomized in GR1 (n=24) and GR2 (n=22). Both groups were comparable with regard to age, height, weight, smoking history, baseline body plethysmography (FVC, FEV1, and RAW), and the severity of COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) staging, respectively. However, the short-term effects of the treatment with regard to FEV1 (2.0 l vs 1.7 l; p=0.031) and increase of FEV1 (0.31 l vs 0.10 l; p=0.02) were better in GR1. More patients in GR1 had an improvement of ≥ 10% in FEV1 (p=0.004) and improvement of the severity of COPD (p=0.012) after the 1-week treatment. Fewer pulmonary complications (11.1% vs 42.9%, p=0.04) were observed in GR1 after surgery. Both therapies resulted in an improvement of lung function. There is benefit from adding inhalative budenoside to tiotropium and formoterol in terms of an improvement in FEV1 and the severity of COPD. These beneficial results might lead to less pulmonary complications in the postoperative period.

To describe treatment patterns, all-cause and migraine-related healthcare resource utilization (HCRU), and direct costs among people with migraine treated with concomitant calcitonin gene-related peptide monoclonal antibody (CGRP mAb) and novel acute migraine medications (ubrogepant, rimegepant, lasmiditan) in the United States (US). This retrospective, observational cohort study utilized data from the IBM MarketScan® Research Databases and included adults initiating CGRP mAb or novel acute migraine medication as index medications between May 01, 2018, and Feb 28, 2021. All-cause and migraine-related HCRU (number of visits) and costs at baseline (12 months pre-index) and at follow-up (12 months post-index) were descriptively analyzed; differences between values at follow-up and baseline were reported. Of 4,167 included in the analysis (mean [SD] age: 43.7 [11.2] years), 89.2% were women, and 59.7% had chronic migraine. Adherence to the indexed CGRP mAb was 47% (using proportion of days covered [PDC]) and 80.1% (using medication possession ratio [MPR]); mean (SD) persistence was 273.4 (115.3) days). At follow-up, 43.9% of the patients discontinued their index preventive medication of which 80.2% switched to a different preventive migraine medication; 17.0% restarted their index preventive medication. Reductions in all-cause inpatient HCRU, all-cause inpatient and outpatient costs, and migraine-related outpatient HCRU were observed at follow-up vs. baseline, whereas increases in all-cause outpatient HCRU, all-cause medication costs, migraine-related inpatient HCRU, and migraine-related inpatient, outpatient, and medication costs were observed. In this study, observed treatment patterns with the indexed CGRP mAb were consistent with prior reports. Concomitant treatment with CGRP mAb and novel acute migraine medications led to reductions in some outcomes of HCRU and direct costs, however, increases were also observed. Treatment utilization, reductions in HCRU and cost savings identified in this study in favor of concomitant CGRP mAb and novel acute medications may help clinicians and other healthcare decision makers assessing appropriate therapeutic options for migraine management.

ObjectiveTo estimate the impact COVID-19 pandemic on healthcare resource utilization (HCRU) among individuals with major depressive disorder (MDD).MethodA retrospective cohort study was conducted to compare HCRU in the twelve months prior to and six months following pandemic onset among 1,318,709 individuals with MDD and propensity-score matched controls. Outcomes were monthly rates of all-cause and MDD-specific outpatient, inpatient, and prescription medication HCRU. Piecewise random effects models were used to adjust for patient-level clustering, trends over time, and pre-pandemic factors.ResultsIn the first month following onset, outpatient HCRU declined with primary care visits down 25.1%. Following this initial decline, outpatient HCRU increased, exceeding pre-pandemic rates within three months. By April 2020, three quarters of all psychotherapy sessions were delivered by telehealth, followed by psychiatry (62.3%), and primary care visits (30.1%). The use of telehealth remained highest for psychotherapy and psychiatry (representing 67.6% and 54.2% of visits, respectively, in September 2020). All-cause partial-day hospitalizations declined 50.5% and remained depressed through July 2020 (down 18.3%). Beginning in the first month post-onset, prescription medication HCRU increased for all antidepressant and antipsychotic medication classes: serotonin modulators ( + 11.8%), bupropion ( + 10.4%), SSRIs ( + 9.0%), SNRIs ( + 8.6%), and atypical antipsychotics ( + 7.5%).ConclusionsFollowing pandemic onset, individuals with MDD realized an immediate, but short-lived, reduction in primary care HCRU. Telehealth use remained elevated through the first six months. The most significant and sustained reduction in HCRU was noted for partial-day hospitalizations and all-cause ED visits.