Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) with ≥ 1 F508del-CFTR allele in Phase 3 clinical trials. ELX/TEZ/IVA treatment led to improved lung function, with increases in percent predicted forced expiratory volume in 1 second (ppFEV₁) and Cystic Fibrosis Questionnaire-Revised respiratory domain score. Here, we evaluated the impact of ELX/TEZ/IVA on the rate of lung function decline over time by comparing changes in ppFEV₁ in participants from the Phase 3 trials with a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry not eligible for cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Participants treated with ELX/TEZ/IVA had on average no loss of pulmonary function over a 2-year period (mean annualized rate of change in ppFEV₁, +0.39 percentage points [95% CI, -0.06 to 0.85]) compared with a 1.92 percentage point annual decline (95% CI, -2.16 to -1.69) in ppFEV₁ in untreated controls. ELX/TEZ/IVA is the first CFTR modulator therapy shown to halt lung function decline over an extended time period.

Introduction Benefits of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) therapy in people with cystic fibrosis (pwCF) may extend beyond the pulmonary system to extrapulmonary complications. This study compared extrapulmonary complication-related healthcare resource utilization (HCRU) prior to and following initiation of ELX/TEZ/IVA. Methods pwCF aged ≥ 6 years newly initiating ELX/TEZ/IVA on or after 10/21/2019 were identified in the Merative™ MarketScan^® Commercial and Multi-state Medicaid Databases. pwCF had continuous coverage with medical and pharmacy benefits for ≥ 1 year prior and following their first prescription fill for ELX/TEZ/IVA treatment. The number of pwCF with ≥ 1 medical claim in any site of care or ≥ 1 inpatient claim with an extrapulmonary condition-related diagnosis and/or procedure code was compared pre- to post-treatment; differences in the proportion of pwCF with ≥ 1 extrapulmonary complication were calculated between the pre- and post-treatment periods. Results The study included 1612 pwCF. A relative reduction of 14.0% in the proportion of people with ≥ 1 extrapulmonary complication claim in any site of care was observed from the pre- to post-treatment period [1209 (75.0%) to 1040 (64.5%), p < 0.001]. Within the inpatient setting, a relative reduction of 64.2% in the proportion of patients with ≥ 1 extrapulmonary complication-related hospitalization was observed [397 (24.6%) pre-treatment to 142 (8.8%) post-treatment, p < 0.001]. The relative reductions in the proportion of people with ≥ 1 claim in any site of care were significant for four of the seven extrapulmonary systems [electrolyte (41.2%), upper respiratory (32.8%), nutritional (28.1%), and lower gastrointestinal (17.8%), all p < 0.001]; relative reductions in the inpatient setting were significant for six of the seven extrapulmonary systems [nutritional (77.2%), lower gastrointestinal (67.3%), upper gastrointestinal (63.9%), upper respiratory (62.9%), cystic fibrosis-related diabetes (57.1%), and electrolyte (39.7%), all p < 0.01]. Conclusions ELX/TEZ/IVA significantly reduced extrapulmonary complication-related HCRU in CF. Findings suggest a multisystemic benefit of ELX/TEZ/IVA treatment in addition to demonstrated transformational benefits on pulmonary function.

This retrospective, longitudinal, observational study evaluated the incidence of opioid use disorder (OUD) among patients newly initiating opioids to manage acute and chronic pain in the United States. Additionally, healthcare resource utilization (HCRU) and associated costs were analyzed. Adult patients newly treated with prescription opioids were identified within the MarketScan administrative claims databases (2016-2018). Patients were classified as experiencing acute or chronic pain based on total prescription pain medication use within one year of the initial opioid prescription. Subgroups of patients with or without OUD were identified using diagnosis codes. The 1-, 2-, and 3-year incidence rates of OUD were 0.21%, 0.32%, and 0.43%, respectively, among acute pain patients and 1.11%, 1.52%, and 1.92% among chronic pain patients. Unadjusted all-cause HCRU were substantially higher among patients with OUD compared to those without OUD over the 12-month period following OUD diagnosis. The associated unadjusted total all-cause healthcare costs were 3.1-times and 2.0-times higher for those with OUD compared to those without OUD in the acute and chronic pain cohorts, respectively. The total all-cause healthcare costs for patients with OUD remained significantly higher, even after adjusting for baseline characteristics. When extrapolated nationally, estimated costs for patients managing acute or chronic pain and newly diagnosed with OUD were $3.3 billion (B) and $5.9B, respectively, totaling $9.2B. Pain medication use was identified using claims for filled prescriptions; patients' actual medication usage and use of over-the-counter medications cannot be ascertained. OUD diagnosis was based on specific ICD-10-CM diagnosis codes, potentially underestimating the true incidence and economic impact. Newly diagnosed OUD following prescription opioid use for managing acute and chronic pain imposes a substantial economic burden within the first year following OUD diagnosis. Increased use of effective non-opioid analgesics may help reduce the incidence and economic burden of OUD.