Observations from a systematic review of pharmacist- led research in solid organ transplantation: An opinion paper of the American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network

IntroductionThe contributions of transplant pharmacists to clinical and translational research in the United States are ill- defined and have not been systematically reviewed.ObjectivesThe American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network conducted a systematic review of available pharmacist- led research publications involving solid organ transplantation with the intent to quantify and describe pharmacist- led research endeavors and their changes over time.MethodsAn electronic search of Scopus was conducted to identify publications in the field of solid organ transplantation by pharmacist authors between January 1, 1975 and May 25, 2017. Articles were excluded if they were written in non- English languages or originated from non- US countries. Review articles, case reports, surveys, basic science research, pre- clinical studies, and non- transplant research were further excluded. Studies were categorized as one of four phases on the clinical and translational research spectrum, adapted from the Harvard Clinical and Translational Science Center description of a T1 to T4 classification system.ResultsA total of 10- 354 publications were identified by the systematic search with 547 full- text English- language publications included in the analysis. Pharmacists served as the first author in 87% of the articles and as the senior author in 67% of the articles. A total of 71% of the articles included more than one pharmacist author. Transplant pharmacists published more studies that employed a retrospective or observational study design (55% and 78%, respectively). A total of 37% of studies were funded. On the spectrum of clinical and translation research, pharmacists were most involved in T3 (translation to practice) research (72%), followed by T2 (translation to patients) research (23%).ConclusionsTransplant pharmacists are increasingly represented in the US literature and frequently published across domains. Further demonstrating the relevance of pharmacist- delivered interventions and outcomes is a critical area of practice focus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/2/jac51294.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/1/jac51294_am.pd

Results of ASERTAA, a randomized prospective crossover pharmacogenetic study of immediate-release versus extended-release tacrolimus in African American kidney transplant recipients

BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile. STUDY DESIGN: Randomized prospective crossover study. SETTING & PARTICIPANTS: 50 African American maintenance kidney recipients on stable IR-Tac dosing. INTERVENTION: Recipients were randomly assigned to continue IR-Tac on days 1 to 7 and then switch to LCPT on day 8 or receive LCPT on days 1 to 7 and then switch to IR-Tac on day 8. The LCPT dose was 85% of the IR-Tac total daily dose. OUTCOMES: Tacrolimus 24-hour AUC (AUC MEASUREMENTS: CYP3A5 genotype, 24-hour tacrolimus pharmacokinetic profiles. RESULTS: ∼80% of participants carried the CYP3A5*1 allele (CYP3A5 expressers). There were no significant differences in AUC LIMITATIONS: This was primarily a pharmacogenetic study rather than an efficacy study; the follow-up period was too short to capture clinical outcomes. CONCLUSIONS: Achieving therapeutic tacrolimus trough concentrations with IR-Tac in most African Americans results in significantly higher peak concentrations, potentially magnifying the risk for toxicity and adverse outcomes. This pharmacogenetic effect is attenuated by delayed tacrolimus absorption with LCPT. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, with study number NCT01962922

Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients

An open-label pilot trial involving 10 patients shows that hepatitis C virus genotype 1–infected kidneys transplanted into HCV-negative recipients, followed by direct-acting antiviral therapy, can result in excellent allograft function with cure of HCV infection. To the Editor: Waiting times for kidney transplants exceed 3 to 5 years in many parts of the United States. 1 Yet more than 500 high-quality kidneys from deceased donors with hepatitis C virus (HCV) infection are discarded annually. 2 , 3 Direct-acting antiviral agents, which are associated with high HCV cure rates and manageable side effects, have created the potential to substantially increase the number of kidney transplants by making HCV-infected kidneys available to HCV-negative candidates on the waiting list. 4 , 5 In this open-label, single-group, pilot trial at the University of Pennsylvania (Transplanting Hepatitis C Kidneys into Negative Kidney Recipients [THINKER]; ClinicalTrials.gov . . 

Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients A Single-Group Trial

Background: Organs from hepatitis C virus (HCV)-infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. Objective: To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. Design: Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897) Setting: Single center. Participants: 20 HCV-negative transplant candidates. Intervention: Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3. Measurements: The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys. Results: The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73m(2); 95% CI for between-group difference, -4.2 to 7.5 mL/min/1.73m(2)) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73m(2); CI for between-group difference, -7.2 to 9.8 mL/min/1.73m(2)). Limitation: Small trial. Conclusion: Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource