Metformin Is Associated With Improved Inflammatory Bowel Disease Outcomes in Patients With Type 2 Diabetes Mellitus: A Propensity-Matched Cohort Study.

BACKGROUND: Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. RESULTS: Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ±â€…12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn's disease (CD) (mean age 56.3 ±â€…12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P < .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P < .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P < .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P < .01). Metformin did not affect risk for surgery in patients with UC. CONCLUSIONS: Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.

Our study shows that metformin is associated with decreased risk of corticosteroids in patients with ulcerative colitis and Crohn's disease and decreased risk of surgery in patients with Crohn's disease.

Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

Polypharmacy as Formal Training and a Model of Practice.

Traditional definitions of polypharmacy may largely not account for the market proliferation of herbal and dietary supplements, cannabis products, or incorporate the new science of pharmacogenomics (PGx). Polypharmacy is encountered by most pharmacists providing patient care in many settings. The "polypharmacist" can assist patients and providers with solving medication-related problems (MRPs) in this new and challenging environment of supplements and cannabis products by utilizing traditional pharmacology and pharmacokinetic principles, including PGx, broadly across many medical disciplines. One may encounter polypharmacy more in the geriatric population, though in an age of supplements and cannabis proliferation, polypharmacy is increasingly being encountered at younger ages. Not only is polypharmacy training at best fragmented in pharmacy curricula, but it may also not account for the above-mentioned products that may use the same metabolic pathways to increase drug interactions and adverse drug reactions (ADRs) regarding prescription medications. Polypharmacy being more formally prioritized in pharmacist training may better prepare pharmacists for commonly encountered polypharmacy and can be a viable model of practice.

High-Evidence, Actionable Phenotype Gene Distribution in a Multispecialty, Tertiary Care Clinic: Potentially Actionable Genes and a Referring Department Profile.

Background There has been a trend in recent years toward individualized medicine. Pharmacogenomics (PGx) is the use of patient-specific genetic variations to guide medication selection and treatment. Objective: The primary objective was to characterize the population of referring department patients and identify the number of high-evidence, actionable phenotype (HEAP) genes in this referred population to help guide marketing efforts to the most applicable patient populations and departments. Practice description: Located in a destination, tertiary care clinic. Providers refer patients to a Pharmacogenomics (PGx) specialist for a comprehensive medication review using their pharmacogenomic results. Practice Innovation: The practice is innovative because it has been using PGx in the pharmacy and medical practices since 2016 and has been routinely developing and incorporating PGx best practice alerts (BPAs) into the electronic medical record (EMR) since 2020. Evaluation Methods Genetic results were analyzed from a 27-gene PGx panel test which tests for both pharmacokinetic and pharmacodynamic genes. High-Evidence Actionable Phenotypes (HEAP) are defined as phenotypes with guideline support that may suggest an action by healthcare provider. Low-Evidence Nonactionable Phenotypes (LENP) are defined as phenotypes that do not recommend action. Results There were 1,236 atypical phenotypes identified in the 154 patients referred. Of the atypical genes, 39.97% were HEAP and 60.03% were LENP. Of the HEAP's identified, the majority came from CYP2D6, VKORC1, and UGT1A1. At least 1 HEAP was found in 98.7% of patients (n=152). Conclusion There are a variety of High Evidence Actionable Phenotypes (HEAPs) with a high likelihood of at least one HEAP gene in every patient. These phenotypes can result in serious safety concerns when combined with a medication impacted by one of these HEAP genes. Thus, referral to a pharmacogenomics consultation service may lead to an overall decrease in morbidity and mortality with potential cost avoidance.

New Pneumococcal Vaccines for Prevention of Invasive Pneumococcal Disease in Adult Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at a high risk of developing invasive pneumococcal infection both before and after they are diagnosed. The Advisory Committee on Immunization Practices now endorses use of 2 new pneumococcal conjugate vaccines, PCV15 (Vaxneuvance) and PCV20 (Prevnar 20), for patients who have never received a pneumococcal conjugate vaccine or those with unknown vaccination history. Previous studies have shown that pneumococcal vaccination can decrease the risk of developing severe pneumococcal disease; therefore, it is important that patients with IBD receive pneumococcal vaccination. This report aims to inform clinicians who care for patients with IBD about the changes in immunization practices, as it pertains to pneumococcal vaccination and provides appropriate direction on administering vaccination series.

Two new pneumococcal vaccines (PCV15 [Vaxneuvance], PCV20 [Prevnar 20]) are now recommended for patients who have not received a pneumococcal conjugate vaccine or those with unknown vaccination history. This report summarizes changes in immunization practices and provides direction on vaccination series for patients with inflammatory bowel disease.

Phenytoin Toxicity with High Dose, Concomitant Ascorbic Acid Dosing.

High dose ascorbic acid may increase risk of phenytoin toxicity. This case report demonstrates high phenytoin levels resulting in adverse drug reactions subsequent to dosing concomitantly with high dose vitamin C, or ascorbic acid (AA), as a precaution against acquiring corona virus (COVID) infection. This patient suffered from a major seizure when he ran out of his phenytoin prescription. Subsequent initiation of phenytoin and later addition of high dose AA resulted in truncal ataxia and falls with bilateral wrist and finger extension weakness. Phenytoin and AA were discontinued, and the patient returned to baseline on a new medication regimen of lacosamide and gabapentin without any other major seizures one year later.

Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient.

Background: Pharmacogenomics (PGx) can provide more precision in determining causation of adverse drug reactions (ADRs) from drug-drug-gene interaction clinical application. Case Summary: Patient was an intermediate CYP2C19 metabolizer on stable therapy taking a low but therapeutic dose of sertraline for depression and anxiety over a period of 20 years. The patient then became hyponatremic and cognitively impaired after addition of cannabidiol (CBD) to this sertraline regimen. The proposed mechanism was drug-drug-gene interaction of CBD further inhibiting the CYP2C19 metabolism of sertraline and increasing drug exposure to produce moderate to severe hyponatremia and subsequent cognitive dysfunction. Practice Implications: Pharmacogenomics (PGx) testing may assist in etiology of patient symptoms from adverse drug reactions (ADRs) or drug-drug interactions by combining these with detection and application of drug-gene interactions. This case shows inhibition of CYP2C19 by CBD to further increase sertraline exposure, producing hyponatremia and subsequent cognitive dysfunction through CYP2C19 phenoconversion by CBD.

Implications of Cannabidiol in Pharmacogenomic-Based Drug Interactions with CYP2C19 Substrates.

This is a patient case exploring the importance of evaluating herbal and dietary supplements and how they may impact drug-drug and drug-gene implications based on pharmacogenomics test results. Even though herbal supplements are considered natural by many patients, which is often the reason for starting them, herbal supplements may still be metabolized by the same pathways as other medications, potentially contributing to drug-drug, drug-herb, and drug-gene interactions, and therefore, potentially impacting a patient's response to medications.

Vaccination of Patients With Inflammatory Bowel Disease During the COVID-19 Pandemic.

Inflammatory bowel disease and the subsequent immunosuppressive regimens used to treat this condition increase the risk for acquiring viral and bacterial infections. Ensuring that patients are up-to-date with their immunizations may help prevent the development of several of these vaccine-preventable diseases. Therefore, it is imperative that gastroenterology providers offer vaccinations to patients or direct vaccination guidance to primary care providers to minimize the risk for vaccine-preventable diseases. To decrease the risk for co-infection in the setting of the coronavirus disease 2019 pandemic and avoid placing any further burden on the health care system, the call to immunize is more important than ever.

Chronic Anticholinergic Toxicity Discovered in a Pharmacogenomics, Polypharmacy Patient.

OBJECTIVE: To report a case of chronic anticholinergic toxicity in a referred, pharmacogenomics (PGx), polypharmacy patient. SUMMARY: The patient is a 67-year-old male who was referred to the polypharmacy service for a PGx consult. This patient has had episodic fever of unknown origin, general cutaneous vasodilation, tremors, jerks, and brain fogginess which have been unexplained. He has seen specialists from infectious disease, rheumatology, endocrinology, and neurology with no contributory condition causing these symptoms, so he was referred for PGx testing and evaluation by the polypharmacy pharmacist. CONCLUSION: This case demonstrates the importance of pharmacist-patient consultations and how a PGx consult may expose polypharmacy medicationrelated problems of greater significance than the PGx indication for the consult. In addition, the case demonstrates positive interprofessional collaboration between pharmacists and physicians to more effectively solve complex medication-related problems that may not be easily diagnosed through objective lab or diagnostic testing.

Tacrolimus-Induced Bradykinesia Secondary to Phenoconversion in an Elderly Post-Bilateral Lung Transplant Patient.

OBJECTIVE: To report pharmacogenomics post-related bradykinesia secondary to phenoconversion in an elderly post-bilateral lung transplant patient.SUMMARY: The patient was a 68-year-old double lung transplant patient taking the immunosuppressant and CYP3A4/5 substrate tacrolimus concomitantly with 2 CYP3A4/5 inhibitor medications, fluconazole and diltiazem. This drug combination post-dosing resulted in debilitating bradykinesia 1-2 hours after dosing, increasing the risk of falls and possible increased mortality and morbidity risk.CONCLUSION: Taking tacrolimus in combination with CYP3A4/5 inhibitors may increase neurologic adverse effects resulting in increased fall and associated increased mortality and morbidity risk.

Conversion Disorder in a Pharmacogenomics, Polypharmacy Patient: Case Report.

Background: Conversion disorder (CD) is a relatively common psychiatric disorder likely encountered by clinical pharmacists but probably not easily identified by pharmacists. Case Summary: This is a patient case where a patient with a tremor was referred to the pharmacist led, polypharmacy, pharmacogenomics (PGx) service to rule out a PGx cause due to medication metabolism. No pharmacologic or PGx cause was found for the tremor which helped support and confirm a diagnosis of CD. Practice Implications: By working collaboratively with psychiatrists, neurologists, physical medicine colleagues, clinical pharmacists may add value to patient care by assisting with diagnoses and appropriate treatment.

Pharmacogenomics Testing Confirmation of Carbamazepine Induced DRESS Reaction of an HLA-A*31:01 Positive, Polypharmacy Patient.

Pharmacogenomics (PGx) melds well with polypharmacy as another tool to identify medication related problems (MRPs) more specifically so they may be solved most effectively. PGx can pre-emptively assist in medication selection, medication dosing or identify better medications for patients already taking a medication. PGx can also confirm suspect medications of causing MRPs such as adverse drug reactions (ADRs) or drug interactions. In this case, PGx testing confirmed presence of a serious human leukocyte antigen (HLA) drug reaction with eosinophilia and systemic symptoms (DRESS) after a suspect medication had been stopped.

Improving Pain Management with Pharmacogenomics: A General Introduction.

Tailoring an individual patient's pain treatment is paramount to decreasing patient suffering and diminishing morbidity. Performing pharmacogenomic (PGx) testing can help guide prescribing decisions for current and future medication therapy by assisting dosage adjustments to increase therapeutic efficacy, decrease adverse drug reactions and avoid potentially ineffective medications. Pharmacogenomics is the study of inherited genetic information that influences drug response. Therapeutic response to pain medications is influenced by several factors including age, sex, body weight, concomitant diseases, compliance, lifestyle, drug interactions and genes. Genes of interest associated with pain medications include cytochrome P450 (CYP) enzymes, OPRM1, COMT, ABCB1, UGT, COX, OPRK1, OPRD1. To properly use PGx results in clinical application requires the healthcare provider to distinguish the difference between types of PGx tests, interpret test results, be familiar with PGx databases to use for prescribing guidance, and evaluate the level of evidence for specific gene-drug associations. This article introduces these concepts to assist the healthcare provider with incorporating PGx into practice to improve pain management.

Pharmacogenomics (PGx) Patient with Mixed Levels of Actionable Variant Evidence.

OBJECTIVE: To demonstrate the types of clinical recommendations a pharmacogenomics pharmacist may make to medical clinicians with regard to medication management to improve therapeutic outcomes based on varied levels of medical literature evidence. SUMMARY: This case demonstrates how a common type of patient seen in a pharmacist practice may present with a varied pharmacogenomic (PGx) profile, how they may benefit from PGx analysis, and how varying levels of medical literature evidence can be used with clinical decision making. CONCLUSION: PGx testing can help avoid adverse drug reactions (ADRs) or medication inefficacy by assisting in the adjustment of current or future medication doses. It can also help predict the best medications to use or those to avoid in advance by eliminating much of the existing dosing or medication selection method of trial and error.

Polypharmacy as a Clinical Pharmacist Specialist Practice.

The objective of this manuscript is to review an ambulatory care pharmacist service that evolved into a pharmacotherapy, polypharmacy service with multiple submodels. The practice is located in a multispecialty, tertiary care, destination medical clinic in Florida. Ambulatory care pharmacist services have evolved to demand expertise in multiple, specialized areas to address the more complex medical issues of the polypharmacy patient. Many of these patients are older than 65 years of age, with broad medical care needs. A number of changes have led to the need for these expanded services: the growth and diversification of pharmacists' ambulatory care services, the multitude of sophisticated medications, the continued direct-to-consumer commercialization, the growth of dietary supplements, and the implementation of pharmacogenomic testing, In addition, new advances in clinical and laboratory technologies make polypharmacy a viable pharmacist clinical specialty. With the broad knowledge base needed for these patients, a polypharmacy pharmacist may function as a pharmacology troubleshooter expert.

Description of an Established, Fee-for-Service, Office-Based, Pharmacist-Managed Pharmacogenomics Practice.

OBJECTIVE: To describe an established, pharmacist-managed, fee-for-service, office-based pharmacogenomics (PGx) practice.
SETTING: Multi-specialty, academic, tertiary care medical clinic and hospital.
PRACTICE DESCRIPTION: Physician office-based PGx fee-for-service (FFS) pharmacist practice. Patients seen are complex and most are older adults.
INNOVATION: Established service in a new area of ambulatory practice that is financially self-sustaining. Patients who received PGx testing were seen within the medication therapy management polypharmacy practice since 2015, with the PGx practice becoming official in 2018.
MAIN OUTCOME MEASUREMENTS: Growth of practice, evaluated by referred patient consults ordered per month by providers.
RESULTS: Because of insufficient third-party payment for PGx services, the practice was developed as a selfpay, FFS practice and growing because of patient and provider demand.
CONCLUSION: It is quite possible pharmacists in greater numbers can expand PGx services into ambulatory and inpatient areas they may have never otherwise entered now that PGx has grown in use and relevance. PGx presents additional opportunities and service lines for pharmacists to practice how they were trained and assist them in collaborative integration onto the medical team.

Methotrexate Central Nervous System Toxicity Identified in a Pharmacogenomics Pharmacist Consult Patient.

OBJECTIVE: To report a possible pharmacogenomics (PGx)-related, cognitive dysfunction, adverse drug reaction from methotrexate (MTX) that may be multifactorial in origin. SUMMARY: The patient subject is a 76-year-old Caucasian female of Russian ancestry suffering from rheumatoid arthritis and treated with MTX who presented to the diagnostic and consultative physician service in a medical clinic with advancing cognitive dysfunction, manifesting as memory loss, dizziness, and confusion. Components of this possible adverse drug reaction (ADR) may include ancestry, pharmacogenomics (PGx) characteristics of the patient, and a change in route of administration, among others. The case demonstrates how patients referred to a pharmacist consult service for a suspected ADR with possible PGx implications may uncover other contributory factors to the ADR. CONCLUSION: PGx testing may increase clinical pharmacist referrals to identify a PGx etiology to an ADR. However, they may also identify other non-PGx contributory factors to an ADR.