Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease

Elchynski, Amanda L; Cicali, Emily J.; Busto, M Castineira; Hamilton, Alessandra; Chang, Ku-Lang; Schmidt, Siegfried; Weiner, Brian; Davis, Richard H.; Estores, David; Smith, D. Max; Wiisanen, Kristin; Cavallari, Larisa H.

doi:10.1038/s41397-021-00244-6

Cited by 8 publications

(9 citation statements)

References 24 publications

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“…These findings support the reusability of PGx results beyond the indication for which they were ordered. Another study of 448 patients with PGx results originally ordered to guide opioid or PPI prescribing found more than 75% of participants were prescribed another PGx medication for the treatment of an unrelated comorbidity 39 . Similarly, two studies published in 2020 showed over half of the patients who were genotyped for CYP2C19 following a percutaneous coronary intervention were prescribed at least one other medication impacted by CYP2C19 40,41 .…”

Section: Discussionmentioning

confidence: 99%

“…Another study of 448 patients with PGx results originally ordered to guide opioid or PPI prescribing found more than 75% of participants were prescribed another PGx medication for the treatment of an unrelated comorbidity. 39 Similarly, two studies published in 2020 showed over half of the patients who were genotyped for CYP2C19 following a percutaneous coronary intervention were prescribed at least one other medication impacted by CYP2C19. 40,41 This is unsurprising, as nearly 70% of older adults have two or more chronic conditions where treatment may involve medications with PGx interactions (e.g., cardiovascular disease and clopidogrel-CYP2C19, depression and SSRIs-CYP2C19, gastroesophageal reflux disease and PPIs-CYP2C19).…”

Section: Alert Response By Care Settingmentioning

confidence: 99%

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Clinician Response to Pharmacogenetic Clinical Decision Support Alerts

Lemke,

Cicali,

Williams

et al. 2023

Clin Pharma and Therapeutics

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The objective of this study was to characterize clinician response following standardization of pharmacogenetic (PGx) clinical decision support alerts at University of Florida (UF) Health. A retrospective analysis of all PGx alerts that fired at a tertiary academic medical center from August 2020 through May 2022 was performed. Alert acceptance rate was calculated and compared across six gene‐drug pairs, patient care setting, and clinician specialty. The disposition of the triggering medication was compared to the alert response and evaluated for congruence. There were a total of 818 alerts included for analysis of alert response, 557 alerts included in acceptance rate calculations, and 392 alerts with sufficient information to assess clinical response. The overall acceptance rate was 63%. The alert response and clinical response were congruent for 47% of alerts. Alert response was influenced by the triggering gene‐drug pair, clinician specialty, patient care setting, and specialty of the provider who initially ordered the PGx test. Clinical response was mostly incongruent with alert response. Alert acceptance is influenced by the triggering gene‐drug pair, clinician specialty, and care setting. Alert response is not a reliable surrogate marker for clinical action. Any future research into the impact of CDS alerts should focus on clinical response rather than alert response. Given the reliance on CDS alerts to enhance uptake of PGx, it is worthwhile to further investigate their impact on prescribing and patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Alert Response By Care Settingmentioning

confidence: 99%

Clinician Response to Pharmacogenetic Clinical Decision Support Alerts

Lemke,

Cicali,

Williams

et al. 2023

Clin Pharma and Therapeutics

Self Cite

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“…Pharmacists trained in PGx are well-positioned as members of interdisciplinary health-care teams to interpret PGx results, recommend actions to mitigate MRPs, and educate clinicians, especially to help guide statin and warfarin therapy [ 9 ]. This case report demonstrates how preemptive PGx testing, while utilizing a clinical decision support system (CDSS), would have identified drug-gene and drug-drug interactions at the time of prescribing, resulting in reduced risk of ADEs [ 11 ]. The aim of this case report was to perform a pharmacogenetic examination in a 70-year woman with polypharmacy and multiple comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic Testing in a 70-Year-Old Woman with Polypharmacy and Multiple Comorbidities: A Case Report

Jessop¹,

Russell²,

DeJesus³

et al. 2023

Am J Case Rep

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Objective:Unknown etiology Background:Comorbidities and polypharmacy are difficult to manage, as polypharmacy hinders identification and prevention of medication-related problems. Risk for adverse drug events (ADEs) can be minimized through pharmacogenomic (PGx) testing and related therapeutic adjustments. Case Report:A 70-year-old woman with comorbidities and medications enrolled in the Program of All-inclusive Care for the Elderly presented with left lower extremity (LLE) pain, generalized weakness, and major depressive disorder. The provider requested a medication safety review, where the clinical pharmacist-recommended PGx testing given the LLE pain and weakness while taking a statin and inconsistent INR readings taking warfarin. The pharmacist recommended switching atorvastatin to pravastatin to minimize the risk for statin-associated ADEs due to CYP3A4 inhibition and switching fluoxetine to citalopram due to uncontrolled depression/anxiety and to mitigate drug-drug interactions with carvedilol to reduce the risk of orthostatic hypotension. Recommendations were accepted and upon follow-up the patient reported minor LLE pain and improved wellbeing on citalopram. Following PGx testing, the patient had decreased function at SLCO1B1 and was an intermediate metabolizer for CYP2C9 and CYP2D6. This case demonstrates how preemptive PGx testing would have identified drug-gene interactions (DGIs) at the time of prescribing and reduced the risk of statin-associated muscular symptoms, highlighting the utility of panel-based PGx testing in older adults at high risk for ADEs and/or therapy failure. Conclusions:Decreased function at SLCO1B1 increases exposure to statins, leading to statin-induced myalgias, as displayed in this case. PGx testing can help identify DGIs, choose optimal therapies in medically complex older adults, and minimize ADE risk.

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“…13,14 In a study of patients with chronic pain or gastroesophageal reflux, most patients were prescribed medications in which pharmacogenomic testing may have guided management. 15 The potential utility of pharmacogenomic assessments for individualizing therapy for patients with DGBI has also been highlighted. 9,16 Although the benefit of pharmacogenomic testing of CYP2D6, CYP2C19, and SLC6A4 variations for guiding treatment of psychiatric diseases has been established, 17 no studies have addressed the utility of pharmacogenomic testing for improving outcomes of patients with DGBI in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, single nucleotide variations in bile acid synthesis and adrenergic‐serotoninergic genes predict the response to colesevelam and clonidine for patients with diarrhea‐predominant IBS 13,14 . In a study of patients with chronic pain or gastroesophageal reflux, most patients were prescribed medications in which pharmacogenomic testing may have guided management 15 . The potential utility of pharmacogenomic assessments for individualizing therapy for patients with DGBI has also been highlighted 9,16 …”

Section: Introductionmentioning

confidence: 99%

Most patients with disorders of gut‐brain interaction receive pharmacotherapy with major or moderate drug‐gene interactions

Varma,

Staab,

Matey

et al. 2023

Neurogastroenterology Motil

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BackgroundHow variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut‐ brain interaction is unclear.AimsTo assess the prevalence of pharmacogenomics‐predicted drug‐gene interactions and symptom outcomes for patients with disorders of gut‐brain interaction.MethodsPatients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium‐ dependent serotonin transporter.ResultsAt baseline, 79 of 94 participants (84%) had at least one predicted major drug‐ gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome‐symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months (p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity (p = 0.03) and pain (p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes (n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations.ConclusionsThe homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut‐brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.

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Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease

Cited by 8 publications

References 24 publications

Clinician Response to Pharmacogenetic Clinical Decision Support Alerts

Clinician Response to Pharmacogenetic Clinical Decision Support Alerts

Pharmacogenetic Testing in a 70-Year-Old Woman with Polypharmacy and Multiple Comorbidities: A Case Report

Most patients with disorders of gut‐brain interaction receive pharmacotherapy with major or moderate drug‐gene interactions

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