Long-term impact of ivacaftor on mortality rate and health outcomes in people with cystic fibrosis.

BACKGROUND: Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US. METHODS: Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator (CFTR) gating mutation (excluding R117H); age-matched comparator cohort included people with a F508del and a minimal function CFTR mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations. FINDINGS: Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV1: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI z-scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m2 and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733). INTERPRETATION: Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term.

A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.

INTRODUCTION: Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. METHODS: This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6 years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1 s (ppFEV1) was estimated over 5 years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. RESULTS: In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5 years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5 years. Findings were generally consistent with those of shorter follow-up periods. CONCLUSION: IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5 years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).

Clinical and Economic Burden in Patients With Systemic Lupus Erythematosus During the First Year After Initiating Oral Corticosteroids: A Retrospective US Database Study.

OBJECTIVE: To characterize health care resource utilization (HCRU), health care costs, and adverse events (AEs) among patients with systemic lupus erythematosus (SLE) initiating oral corticosteroids (OCS) versus patients without OCS use. METHODS: In this retrospective cohort study (GSK Study 213061), eligible patients (aged ≥5 years at first OCS claim) with SLE from the IQVIA Real-World Data Adjudicated Claims-US database (January 2006 to July 2019) had continuous enrollment during the 6-month preindex (baseline) and 12-month postindex (observation) periods and one or more inpatient or emergency department SLE diagnosis codes or two or more outpatient SLE diagnosis codes during baseline. The "OCS-initiator cohort" comprised patients with one or more OCS pharmacy claims during the study period and no evidence of preindex OCS use and was classified into three exposure categories based on the number of 6-month periods of more than 5 mg/day of OCS use (0, 1, 2). The "no-OCS-use cohort" comprised patients without OCS claims, although patients may have received OCS prior to the study period. Clinical and economic outcomes were reported over the observation period. RESULTS: Adjusted health care costs differed significantly ($6542 [95% confidence interval (CI): $5761-$7368], $19,149 [95% CI: $16,954-$21,471], $28,985 [95% CI: $25,546-$32,885]). HCRU incidence rates were significantly greater for all OCS-initiator exposure categories (n = 16,216) versus the no-OCS-use cohort (n = 11,137; adjusted incidence rate ratios [95% CI]: 1.22 [1.19-1.24], 1.39 [1.34-1.43], 1.66 [1.60-1.73]). OCS-related AEs were experienced by 67.1% to 74.1% of patients with OCS initiation, most commonly affecting the immune system. CONCLUSION: Within 12 months of OCS initiation, patients with SLE experienced substantial clinical and economic burden, which may imply a need to minimize OCS use.

Prolonged oral corticosteroid treatment in patients with systemic lupus erythematosus: An evaluation of 12-month economic and clinical burden.

BACKGROUND: Prolonged, high-dose corticosteroid treatment for systemic lupus erythematosus (SLE) is associated with substantial health care costs, health care resource utilization (HCRU), and adverse events (AEs). OBJECTIVE: To compare all-cause health care costs, HCRU, and oral corticosteroid (OCS)-related AEs among patients with prevalent OCS use and patients without OCS use. METHODS: This retrospective, longitudinal cohort study (GSK study 214100) used claims data from the IQVIA Real-World Data Adjudicated Claims - US, IQVIA, Inc, database between January 1, 2006, and July 31, 2019, to identify patients with SLE. Patients with at least 1 OCS pharmacy claim during the study period and continuous OCS use during the 6-month pre-index (baseline) period (index date is the date of the first OCS claim following 6 months' continuous use) formed the "prevalent OCS use cohort." This cohort was subdivided based on the level of OCS exposure during the 12-month observation period, ie, the number of 6-month periods of greater than 5 mg/day OCS use (0, 1, or 2). Patients without OCS claims formed the "no OCS use cohort." All patients had continuous enrollment during the baseline and observation periods, had at least 1 inpatient or at least 2 outpatient SLE diagnosis codes during baseline, and were aged at least 5 years at index. A 2-part model, a generalized linear regression model with a negative binomial distribution, and a multivariate logistic regression model were used to compare health care costs, HCRU, and the odds of developing an OCS-related AE between cohorts, respectively. RESULTS: The no OCS use and prevalent OCS use cohorts included 21,517 and 16,209 patients, respectively. Adjusted health care cost differences (95% CI) were significantly lower for the no OCS use cohort vs all prevalent OCS use exposure categories ($5,439 [$4,537-$6,371] vs $17,856 [$16,368-$19,498]), driven by inpatient stays and outpatient visits; HCRU was also significantly lower (adjusted incidence rate ratios vs no OCS use cohort [95% CI]: 1.20 [1.16-1.23] vs 1.47 [1.41-1.52]). Health care costs and HCRU increased with increasing length of OCS exposure. OCS-related AEs occurred more frequently for all prevalent OCS use exposure categories vs the no OCS use cohort (odds ratio [95% CI]: 1.39 [1.25-1.55] vs 2.32 [2.02-2.68]), driven by hematologic/oncologic and immune system-related AEs. The mean (SD) average daily dose of OCS increased with increasing periods of prevalent OCS use (2.5 [1.3], 6.9 [31.1], and 34.6 [1,717.3] mg/day, respectively, for patients with 0, 1, and 2 periods of OCS use). CONCLUSIONS: Prevalent OCS use incurs a substantial clinical and economic burden, highlighting the need for restricted OCS doses and durations. DISCLOSURES: This study (GSK Study 214100) was funded by GSK. GSK was involved in designing the study, contributing to the collection, analysis, and interpretation of the data, supporting the authors in the development of the manuscript, and funding the medical writing assistance. All authors, including those employed by GSK, approved the content of the submitted manuscript and were involved in the decision to submit the manuscript for publication. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group, which received research funding from GSK to conduct this study. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Mr Bell is an employee of GSK and holds stocks and shares in the company. Ms Averell and Dr Huang are former employees of GSK and held stocks and shares in the company at the time of the study.

A 5-Year Retrospective, Observational Study Assessing Rheumatoid Arthritis Disease Outcome Measures to Characterize Systemic Lupus Erythematosus Burden in the USA.

INTRODUCTION: We evaluated the use of rheumatoid arthritis (RA) disease measures in patients with systemic lupus erythematosus (SLE) in a US community-based rheumatology physician network over 5 years. METHODS: This retrospective, observational cohort study (GSK Study 213818) of patients with SLE utilized electronic medical records (01 January 2010-31 December 2019) from the United Rheumatology Normalized Integrated Community Evidence database. The index was the date of first SLE diagnosis recorded in the database; the observation period was 5 years post-index. RA disease measures evaluated were: Pain Index, Multi-Dimensional Health Assessment Questionnaire (MD-HAQ), Patient Global Assessment (PtGA), Physician Global Assessment (PGA), Swollen Joint Count (SJC), Tender Joint Count (TJC), Routine Assessment of Patient Index Data 3 (RAPID3), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score 28 (DAS-28). The number of patients with measures utilized, the score on each measure, and proportion of patients per disease activity category were assessed. RESULTS: Overall, 5990 patients with SLE were included. The most frequently used measures were Pain Index, SJC, TJC, MD-HAQ, PtGA, RAPID3, and PGA (cumulative use over Years 1-5: 23.9-71.3%). For all measures, frequency of use was lowest in Year 1, followed by a general increase from Year 1 to Year 5. Scores remained relatively stable for most measures, and the proportion of patients in remission or with low/moderate disease activity per RAPID3 increased. CONCLUSION: RA disease measure utilization in SLE was generally infrequent but increased over time. Pain Index and MD-HAQ were the most commonly applied cumulatively across 5 years of follow-up. The rationale for the increased use of these measures in SLE over time requires further exploration. In the absence of a clinically applicable SLE-specific measure, the use of RA measures, for example in conjunction with SLE measures, may provide an alternative approach for measuring disease activity, representing an opportunity to improve patient outcomes.

Health Care Costs With Sustained Oral Corticosteroid Use in Systemic Lupus Erythematosus.

PURPOSE: The goal of this study was to compare health care costs, health care resource utilization, and adverse events associated with sustained oral corticosteroid (OCS) use versus no OCS use in systemic lupus erythematosus. METHODS: This retrospective cohort study used claims data (January 1, 2006-July 31, 2019) from patients with systemic lupus erythematosus aged ≥5 years with ≥24 months of continuous enrollment. Health care costs, health care resource utilization, and OCS-related adverse events were assessed. The sustained OCS cohort (defined as ≥12 months of continuous OCS use) was divided into exposure categories based on the number of 6-month classification periods with >5 mg/d OCS (0, 1-2, or 3-4). FINDINGS: Of the 6234 patients in the sustained OCS use cohort, there were 1587 (25.5%) patients with 0 periods of >5 mg/d OCS use, 2087 (33.5%) patients with 1 to 2 periods of >5 mg/d OCS use, and 2560 (41.1%) patients with 3 to 4 periods of >5 mg/d OCS use; the no OCS use cohort included 7828 patients. Adjusted health care cost differences (95% CIs) were significantly greater for patients with 0, 1 to 2, and 3 to 4 periods of OCS use >5 mg/d versus the no OCS use cohort ($7774 [5426-10,223], $21,738 [18,898-25,321], and $30,119 [26,492-33,774], respectively). A higher proportion of patients in all OCS exposure categories required health care resource utilization (≥99.7% vs 93.4%) and experienced OCS-related adverse events (94.3%-96.8% vs 82.6%) versus the no OCS use cohort, with more periods of OCS use >5 mg/d associated with increased health care resource utilization and adverse events. IMPLICATIONS: Sustained OCS use in systemic lupus erythematosus was associated with high economic burden, health care resource utilization, and OCS-related adverse events. These data highlight the need for health care providers to carefully consider OCS use in systemic lupus erythematosus.

Suicidal ideation and attempts in the United States of America among stimulant-treated, non-stimulant-treated, and untreated patients with a diagnosis of attention-deficit/hyperactivity disorder.

BACKGROUND: Studies of the association between attention-deficit/hyperactivity disorder (ADHD) drug therapy and suicidal ideation and attempts (SIA) have conflicting results. METHODS: Cohorts of patients with ADHD aged 6 years or older with at least one pharmacy claim for a central nervous system (CNS) stimulant or a non-stimulant, or with no claims for ADHD pharmacotherapy, were identified in the US IBM® MarketScan® Research Database from January 2008 to March 2018. Incidence density rates (IDRs) of SIA (i.e., claims for suicide and self-inflicted poisoning, suicide and self-inflicted injuries, or suicidal ideation) were calculated. Cohorts were compared (CNS stimulants vs non-stimulants; CNS stimulants vs no pharmacotherapy) using hazard ratios (HRs) estimated from Cox proportional hazards models. Inverse-probability-of-treatment weighting (IPTW) was used to control for confounding. RESULTS: The study included 797,189 patients (CNS stimulants, 622,536; non-stimulants, 54,615; no pharmacotherapy, 120,038). IDRs of SIA (per 1000 patient-years) were: CNS stimulants, 5.8; non-stimulants, 10.5; and no pharmacotherapy, 10.0. The overall SIA risk was significantly lower with CNS stimulants than with non-stimulants (IPTW-adjusted HR = 0.70, 95% confidence interval = 0.61-0.81, p < 0.001) and no pharmacotherapy (0.62, 0.57-0.67, p < 0.001). LIMITATIONS: SIA assessment was based on diagnostic codes; suicidal ideation may not have been reported; completed suicides were generally not captured; and treatment was not verified. CONCLUSIONS: In this population-based study of patients with ADHD, SIA risk was significantly lower in those receiving CNS stimulants relative to those receiving non-stimulants or no pharmacotherapy, suggesting that CNS stimulants may attenuate SIA risk.