Survival in Pulmonary Arterial Hypertension Patients Awaiting Transplant

Gomberg‐Maitland, Mardi; Glassner-Kolmin, Cherylanne; Watson, Sandra; Frantz, R.P.; Park, M.; Frost, Adaani E.; Benza, Ray; Torres, Fernando

doi:10.1016/j.healun.2013.01.314

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For those patients who have a poor response by way of adverse effects or lack of benefit, the time lost to inadequate treatment leads to further disease progression. 1,2 Matching an individual patient to the medication likely to be most effective is the promise of precision medicine. 31 This concept is not new to PAH, as a notable example includes the use of calcium channel blockers for patients with a positive vasoreactivity test.…”

Section: Discussionmentioning

confidence: 99%

“…1 Despite a rapid expansion of treatments approved over the last two decades, long-term outcomes remain unsatisfactory. 2 Prostacyclins are a mainstay of treatment for patients with more advanced symptoms of PAH. 3 Treprostinil is a prostacyclin analog approved for the treatment of PAH and available in several different routes of administration, including subcutaneous, intravenous, inhalation, and oral.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A pilot study of oral treprostinil pharmacogenomics and treatment persistence in patients with pulmonary arterial hypertension

Coons

Crisamore

et al. 2021

Ther Adv Respir Dis

View full text Add to dashboard Cite

Background and aims: Treprostinil is a prostacyclin analog used to treat pulmonary arterial hypertension. Dosing is empiric and based on tolerability. Adverse effects are common and can affect treatment persistence. Pharmacogenomic variants that may affect treprostinil metabolism and transport have not been well-characterized. We aimed to investigate the pharmacogenomic sources of variability in treatment persistence and dosing. Methods: Patients were prospectively recruited from an IRB approved biobank registry at a single pulmonary hypertension center. A cohort of patients who received oral treprostinil were screened for participation. Pharmacogenomic analysis was for variants in CYP2C8, CYP2C9, and ABCC4. A retrospective review was conducted for demographics, clinical status, dosing, and response. Fisher’s exact test was used for categorical data and Kruskal–Wallis test or Wilcoxon rank sum were used for continuous data. Results: A total of 15 patients received oral treprostinil and were consented. Their median age was 53 years, 73% were female, and 93% were White. The median total daily dose was 22.5 mg (13.5, 41) at last clinical observation. 40% of patients discontinued treatment with a majority due to adverse effects. Approximately 27% of patients had a loss-of-function variant in CYP2C8 (*1/*3 or *1/*4), whereas 47% of patients had a loss-of-function variant in CYP2C9 (*1/*2, *1/*3, or *2/*2). Minor allele frequencies for ABCC4 (rs1751034 and rs3742106) were 0.17 and 0.43, respectively. Survival analysis showed that increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation [hazard ratio (HR): 0.13; 95% confidence interval (CI): 0.02, 0.91; p = 0.04]. Genetic variants were not significantly associated with dosing. Conclusion: Genetic variants responsible for the metabolism and transport of oral treprostinil were common. Increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation. However, dosing was not associated with genetic variants in metabolizing enzymes for treprostinil. Our findings suggest significant variability in treatment persistence to oral treprostinil, with pharmacogenomics being a potentially important contributor. The reviews of this paper are available via the supplemental material section.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%