Shah Sonam N, Gammal Roseann S, Amato Mary G, Alobaidly Maryam, Reyes Dariel Delos, Hasan Sarah, Seger Diane L, Krier Joel B, Bates David W
Department of Internal Medicine, Brigham and Women's Hospital, 41 Avenue of Louis Pasteur, Office 103, Boston, MA, 02115, USA.
Department of Pharmacy Practice, MCPHS University School of Pharmacy, Boston, MA, USA.
Drug Saf. 2021 May;44(5):601-607. doi: 10.1007/s40264-021-01050-6. Epub 2021 Feb 23.
Medication-related harm represents a significant issue for patient safety and quality of care. One strategy to avoid preventable adverse drug events is to utilize patient-specific factors such as pharmacogenomics (PGx) to individualize therapy.
We measured the number of patients enrolled in a health-system biobank with actionable PGx results who received relevant medications and assessed the incidence of adverse drug events (ADEs) that might have been prevented had the PGx results been used to inform prescribing.
Patients with actionable PGx results in the following four genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines were identified: HLA-A31:01, HLA-B15:02, TPMT, and VKORC1. The patients who received interacting medications (carbamazepine, oxcarbazepine, thiopurines, or warfarin) were identified, and electronic health records were reviewed to determine the incidence of potentially preventable ADEs.
Of 36,424 patients with PGx results, 2327 (6.4%) were HLA-A31:01 positive; 3543 (9.7%) were HLA-B15:02 positive; 2893 (7.9%) were TPMT intermediate metabolizers; and 4249 (11.7%) were homozygous for the VKORC1 c.1639 G>A variant. Among patients positive for one of the HLA variants who received carbamazepine or oxcarbazepine (n = 92), four (4.3%) experienced a rash that warranted drug discontinuation. Among the TPMT intermediate metabolizers who received a thiopurine (n = 56), 11 (19.6%) experienced severe myelosuppression that warranted drug discontinuation. Among patients homozygous for the VKORC1 c.1639 G>A variant who received warfarin (n = 379), 85 (22.4%) experienced active bleeding and/or international normalized ratio (INR) > 5 that warranted drug discontinuation or dose reduction.
Patients with actionable PGx results from a health-system biobank who received relevant medications experienced predictable ADEs. These ADEs may have been prevented if the patients' PGx results were available in the electronic health record with clinical decision support prior to prescribing.
药物相关损害是患者安全和医疗质量的一个重大问题。避免可预防的药物不良事件的一种策略是利用患者特异性因素，如药物基因组学（PGx）来实现个体化治疗。
我们统计了健康系统生物样本库中具有可操作PGx结果且接受了相关药物治疗的患者数量，并评估了如果将PGx结果用于指导处方开具，可能预防的药物不良事件（ADEs）的发生率。
根据临床药物基因组学实施联盟（CPIC）指南，确定了在以下四个基因中具有可操作PGx结果的患者：HLA - A31:01、HLA - B15:02、TPMT和VKORC1。识别出接受相互作用药物（卡马西平、奥卡西平、硫嘌呤或华法林）的患者，并查阅电子健康记录以确定潜在可预防的ADEs的发生率。
在36424例有PGx结果的患者中，2327例（6.4%）HLA - A31:01呈阳性；3543例（9.7%）HLA - B15:02呈阳性；2893例（7.9%）为TPMT中间代谢者；4249例（11.7%）为VKORC1 c.1639 G>A变异的纯合子。在接受卡马西平或奥卡西平的HLA变异阳性患者中（n = 92），4例（4.3%）出现皮疹，需要停药。在接受硫嘌呤的TPMT中间代谢者中（n = 56），11例（19.6%）出现严重骨髓抑制，需要停药。在接受华法林的VKORC1 c.1639 G>A变异纯合子患者中（n = 379），85例（22.4%）出现活动性出血和/或国际标准化比值（INR）>5，需要停药或减量。
健康系统生物样本库中具有可操作PGx结果且接受相关药物治疗的患者经历了可预测的ADEs。如果在开具处方前，患者的PGx结果可在带有临床决策支持的电子健康记录中获取，这些ADEs可能会被预防。
