Real-world association between nonadherence to pulmonary arterial hypertension medications and clinical outcomes in the us

SESSION TITLE: Health Disparities in Pulmonary Hypertension SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:55 pm - 01:40 pm PURPOSE: PAH is a chronic progressive disease without a cure. Treatment nonadherence can negate the clinical benefit of available therapeutic options. We investigated the impact of nonadherence on PAH-related emergency department (ED) visits, hospitalizations, mechanical ventilation (MV), all-cause mortality, and a composite outcome (i.e., any outcome) by each treatment class; and new initiations of intravenous (IV) prostacyclin pathway agents (PPA) in non-parenteral PPA users. METHODS: This was a retrospective cohort study using Komodo US claims data from 1/2015–5/2022 to identify patients newly initiated on PAH medications. Index date was 60 days after first PAH therapy post-PAH diagnosis. Patients on multiple index classes were assigned to a class in the following order: parenteral PPA, oral PPA, endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) stimulators, and phosphodiesterase type-5 inhibitors (PDE5i). Adults with continuous insurance enrollment for 12 months prior to index (baseline) were included; those with pulmonary endarterectomy, balloon pulmonary angioplasty, lung transplant, or atrial septostomy during baseline were excluded to remove patients with chronic thromboembolic pulmonary hypertension. Index therapeutic class adherence was assessed by proportion of days covered (PDC≥80%; proportion of time patient has medication available) while persistent to index class (no gaps ≥60 days). Follow-up was censored at plan disenrollment, death, or study end. Stepwise multivariable Cox models adjusting for payer type and combination therapy were used to assess the effect of nonadherence (daily time-varying cumulative PDC) on outcomes within therapeutic class. Adjusted hazard ratios (HR) and 95% CI were reported. RESULTS: 7565 adults were identified (mean age 60 years; 65% female). Index therapies included PDE5i (65.4%; 17.8% nonadherent), ERA (22.2%; 11.6%), parenteral PPA (6.1%; 8.2%), oral PPA (2.7%; 11.9%), and sGC stimulators (3.5%; 20.8%). Nonadherence was associated with an increased risk of death in PDE5i (HR=3.14, p<0.001) and ERA users (HR=3.19, p<0.001); PAH-related ED visits in PDE5i (HR=2.10, p<0.001) and parenteral PPA users (HR=2.23, p=0.006); PAH-related hospitalization in ERA users (HR=1.49, p=0.01); and composite outcome in all classes except sGC stimulators (range HR=1.26-1.96; all p<0.05). Nonadherence to monotherapy ERA was associated with an increased risk of MV (HR=2.96, p=0.009). CONCLUSIONS: Nonadherence to PDE5i, ERA, or PPA therapy increased the risk of poor clinical outcomes in PAH patients, particularly in PDE5i and ERA patients where nonadherence increased the risk of death three-fold. CLINICAL IMPLICATIONS: Education and shared decision-making should highlight the importance of adherence to decrease nonadherence risk, given the strong relationship between adherence and outcomes. DISCLOSURES: Employee relationship with Cytel Please note: Jan 2022 to present Added 04/03/2023 by Nicole Croteau, source=Web Response, value=Salary Consultant relationship with Natera Please note: 1/14/2022-6/15/2022 Added 03/10/2023 by Teresa De Marco, source=Web Response, value=Consulting fee My spouse/partner as a Research =study PI relationship with Trio Health Please note: 5/1/2019-7/31/2020 Added 03/10/2023 by Teresa De Marco, source=Web Response, value=Grant/Research Support My spouse/partner as a Study PI relationship with CareDx Please note: 5/25/2019-5/31/2025 Added 03/10/2023 by Teresa De Marco, source=Web Response, value=reasearch support for conduct of study My spouse/partner as a researcher relationship with Acceleron Please note: 8/5/2018-12/31/2022 Added 03/10/2023 by Teresa De Marco, source=Web Response, value=Grant support for clinical trial Consultant relationship with Scope-Bial Please note: 2019-2022 Added 03/10/2023 by Teresa De Marco, source=Web Response, value=Consulting fee Consultant relationship with NXT Please note: 2020-present Added 03/10/2023 by Teresa De Marco, source=Web Response, value=Consulting fee Consultant relationship with Aerovate Please note: 11/8/21 to present Added 11/09/2022 by Teresa De Marco, source=Web Response, value=Consulting fee Consultant relationship with Pulnovo Please note: 9/1/22 to present Added 11/09/2022 by Teresa De Marco, source=Web Response, value=Consulting fee Research PI relationship with Acceleron Please note: >$100000 by Teresa De Marco, value=Grant/Research Removed 03/10/2023 by Teresa De Marco, source=Web Response My spouse/partner as a Research grant relationship with Pfizer Please note: 8/2/2016-6/30/2022 Added 03/10/2023 by Teresa De Marco, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Novartis Please note: $5001 - $20000 by Teresa De Marco, value=Honoraria Removed 03/10/2023 by Teresa De Marco, source=Web Response Consultant relationship with Boston Scientific Please note: 2010-present Added 03/10/2023 by Teresa De Marco, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2 years Added 03/10/2023 by Teresa De Marco, value=Consulting fee Consultant relationship with Actelion/Janssen/J&J Please note: >10 years Added 03/10/2023 by Teresa De Marco, value=Consulting fee Consultant relationship with Tectonic Please note: 12/2022 to present Added 03/31/2023 by Teresa De Marco, source=Web Response, value=Consulting fee Employee relationship with Janssen Pharmaceuticals Please note: 9/2018 to now Added 04/04/2023 by Gurinderpal Doad, source=Web Response, value=Salary Advisory Committee Member relationship with Actelion Please note: several years to pre by Harrison Farber, value=Consulting fee Advisory Committee Member relationship with Atlavant Please note: ~2yrs (to present) by Harrison Farber, value=Consulting fee Advisory Committee Member relationship with Acceleron Please note: ~3yeas (to present) by Harrison Farber, value=Consulting fee Advisory Committee Member relationship with Aerovate Please note: ~1yr (to present) Added 03/30/2023 by Harrison Farber, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: many years (to prese by Harrison Farber, value=Consulting fee Advisory Committee Member relationship with Aerami Please note: 6mo to present Added 03/30/2023 by Harrison Farber, value=no fees yet Stock Holder relationship with Johnson and Johnson Please note: 12/13/2021-curr Added 03/24/2023 by Hayley Germack, source=Web Response, value=Stock Holder Employee relationship with Janssen Scientific Affairs, LLC Please note: 12/13/2021-curr Added 03/24/2023 by Hayley Germack, source=Web Response, value=Salary Employee relationship with Janssen Please note: May 2020 to present by Sumeet Panjabi, value=Ownership interest Employee relationship with Janssen Please note: May 2020 to present by Sumeet Panjabi, value=Salary Employee relationship with Cytel, Inc. Please note: 9/28/2021- present Added 04/02/2023 by Jason Simeone, source=Web Response, value=Salary Employee relationship with Cytel Please note: July 2022 to current Added 04/03/2023 by Fei Tang, source=Web Response, value=Salary Employee relationship with Janssen Please note: Nov 2020 to now Added 04/13/2023 by Carly Worden, source=Web Response, value=Salary