Real-World Treatment Patterns Among Patients with Connective Tissue Disorder-Related Pulmonary Arterial Hypertension in the United States: A Retrospective Claims-Based Analysis.

INTRODUCTION: Connective tissue disorders (CTDs) are the most frequent diseases associated with pulmonary arterial hypertension (PAH). Despite advances in treatment, the prognosis of CTD-related PAH remains poor. To help identify areas for improvement in the management of CTD-related PAH, this study assessed real-world PAH treatment patterns in this population in the US. METHODS: Eligible adult patients with PAH initiated on a PAH treatment (index date: 1st initiation date) were identified from Optum's de-identified Clinformatics® Data Mart Database (10/01/2015-09/30/2021) and categorized into mutually exclusive cohorts (CTD + PAH; PAH) based on the presence of CTD diagnosis claims. Treatment patterns were assessed from the index date to the earliest of death or end of continuous insurance eligibility, or data availability. Treatment persistence was assessed using Kaplan-Meier analysis. RESULTS: A total of 4751 patients were included (CTD + PAH: n = 728, mean follow-up of 18.8 months; PAH: n = 4023, mean follow-up of 19.6 months). For both cohorts, the most common first treatment regimens were sildenafil (CTD + PAH: 38.7%; PAH: 51.5%), tadalafil (10.0%; 9.4%), and macitentan (8.1%; 5.4%) monotherapy; these were also the most frequent agents included in any of the first 3 treatment regimens. Combination therapy was more frequent in the CTD + PAH versus PAH cohort (any regimen: 40.9% vs. 27.2%; 1st treatment regimen: 26.9% vs. 18.5%; 2nd: 52.8% vs. 42.0%; 3rd: 55.2% vs. 48.5%). Treatment persistence was similar across cohorts and the first three treatment regimens, with persistence rates ranging from 42.6 to 49.7% at 12 months. CONCLUSIONS: Treatment patterns were generally similar between the CTD + PAH and PAH cohorts, although combination therapy was more frequent in the CTD + PAH cohort. Both cohorts may benefit from broader use of all available PAH treatment classes, including combination therapy. Considering the life-threatening nature of PAH, our findings also highlight the need to address the low persistence rates with PAH therapies regardless of etiology.

Economic burden of illness among patients with pulmonary arterial hypertension (PAH) associated with connective tissue disorders (CTD).

Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue disorders (CTDs). This study provides a contemporary assessment of the economic burden of CTD + PAH and PAH in the United States. Eligible adult patients identified from Optum's deidentified Clinformatics® Data Mart Database (10/01/2015-09/30/2021) were classified into mutually exclusive cohorts based on recorded diagnoses: (1) CTD + PAH, (2) PAH, (3) CTD, (4) control without CTD/PAH. The index date was a randomly selected diagnosis date for PAH (CTD + PAH, PAH cohorts) or CTD (CTD cohort), or a random date (control cohort). Entropy balancing was used to balance characteristics across cohorts. Healthcare costs and healthcare resource utilization (HRU) per patient per month (PPPM) were assessed for ≤12 months postindex and compared among balanced cohorts. A total of 552,900 patients were included (CTD + PAH: n = 1876; PAH: n = 8177; CTD: n = 209,156; control: n = 333,691). Average total all-cause costs were higher for CTD + PAH than PAH cohort ($16,854 vs. $15,686 PPPM; p = 0.02); both cohorts incurred higher costs than CTD and control cohorts ($4476 and $2170 PPPM; all p < 0.001). Average HRU PPPM was similar between CTD + PAH and PAH cohorts (inpatient stay: 0.15 vs. 0.15, outpatient visits: 4.23 vs. 4.11; all p > 0.05), while CTD and control cohorts incurred less HRU (inpatient stay: 0.07 and 0.03, outpatient visits: 2.67 and 1.69; all p < 0.001). CTD + PAH and PAH are associated with a substantial economic burden. The incremental burden attributable to PAH versus the general population and patients with CTD without PAH highlights significant unmet needs among PAH patients.

Content Analysis of 2012-2019 FDA Warning Letters and Notices of Violations using the Economic, Clinical, and Humanistic Outcomes (ECHO) Model.

OBJECTIVE: The study purpose was to critically review FDA-issued warning letters (WLs) and notice of violation (NOV) letters against drug companies' from 2012-2019 for economic, clinical, and humanistic (ECHO) claims made in pharmaceutical promotional materials. Specific objectives were to assess the, (1) number of WLs and NOV issued; (2) frequency of WLs and NOV by therapeutic areas; (3) type of communication media cited in WLs or NOV; (4) intended audience for the claims in promotional materials for which the WLs and NOV were issued; and (5) number of WLs and NOV for ECHO claims. METHODS: The quantitative content analysis approach was employed to review WLs and NOVs, obtained from the FDA website, from January 2012-December 2019. A data abstraction form was created based on the published literature on this topic and assessment of the content of WLs and NOVs for 2010. This form was pilot tested on letters issued in 2011. The researchers discussed any unclear question or information presented in the letters. The letters were reviewed three researchers. If there was disagreement between the reviewers, either a fourth reviewer arbitrated on the disagreement or the letter(s) were discussed by the researchers to determine a final classification. ICD-10 codes were used for therapeutic categories in the data collected form. Descriptive statistics, Kappa statistics for interrater reliability, and Cochrane-Armitage test were performed using IBM SPSS Statistics version 24.0. RESULTS: A total of 102 letters were analyzed. Of these, 19 (19%) were WLs and 83 (81%) were NOVs. Majority of these letters were issued to manufacturers of therapeutic agents for diseases of the nervous system (n=15; 14.7%) and neoplasms (n=15; 14.7%). The most commonly cited media for violation was online website (n=29; 27.1%). Out of the 153 violations in 102 letters, 92 (60.1%) were clinical; 13 (8.5%) humanistic; 2 (1.3%) were economic; and 46 (30%) were categorized as 'Others'. CONCLUSION: The study found misleading claims of the clinical effectiveness and risk information included in the promotional materials targeted to consumers as well as healthcare providers. Promoting reliable, evidence-based information is important for the health of the public as inadequate information could lead to irrational decision making both on consumer as well as on prescriber side.

Continuous Glucose Monitoring: A Review of Available Systems.

Continuous glucose monitoring offers patients with diabetes a new option for monitoring their glucose levels on a regular basis, without the need for perpetual finger-sticks and myriad supplies.