The expanded role of the transplant pharmacist: A 10-year follow-up.

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.

A multicenter case series documenting Medicare Part D plan denials of immunosuppressant drug coverage for organ transplant recipients.

Medicare Part D plans make coverage decisions according to FDA-labeled indications and off-label uses endorsed by two CMS-recognized compendia. Patients who rely on Medicare Part D for immunosuppressive drug coverage are at risk for denied coverage when these medications are prescribed off-label. The purpose of this multicenter collaboration was to assemble a case series documenting situations where immunosuppressive therapies prescribed for transplant patients were denied by Medicare Part D prescription drug plans. This case series documents 66 instances in 39 patients where immunosuppressive drug claims were denied coverage due to off-label use not endorsed by the compendia. Patients were recipients of lung (n = 28, 72%), heart (n = 7, 18%), or liver (n = 4, 10%) transplants. Denied claims were for mycophenolate mofetil (n = 22, 33%), azathioprine (n = 18, 27%), sirolimus (n = 15, 23%), mycophenolate sodium (n = 5, 8%), everolimus (n = 5, 8%), and belatacept (n = 1, 1%). Most denials were upheld across all the levels of attempted appeal, including those escalated to a Medicare Administrative Law Judge. This case series demonstrates a critical flaw in the construct of the Medicare Prescription Drug Benefit. The currently referenced compendia are not up to date and do not reflect best practices in organ transplantation.

Meeting report: Consensus recommendations for a research agenda to address immunosuppressant nonadherence in organ transplantation.

Despite advances in the field of transplantation, immunosuppressant medication nonadherence (NA) remains a primary contributor to suboptimal long-term outcomes. Due to the multidimensional and multifactorial causes of medication NA, studies to date have focused on individual differing facets or single point barriers of NA with relative success. However, these successes have not proven to be sustainable, partly due to the intense resources needed for continued viability. This article provides a summary of a 2-day meeting held in April 2017 (Chicago, IL) prior to the American Transplant Congress in which a multidisciplinary group convened to identify the unmet research needs related to medication NA in transplantation. Thought leaders in the field presented the past, present, and future directions of medication NA with the primary outcome of designing, developing, and ranking targeted interventions into a dynamic research agenda to identify which interventions maintained effects over time. Break-out sessions were created based on the five World Health Organization (WHO) dimensions of adherence. Participants were then organized into the newly formed AST Transplant Pharmacy Adherence Consortium (AST TPAC) research group. This meeting report summarizes the content of the symposium, and the development, background, and future directions of the AST TPAC.

Transplant recipients are vulnerable to coverage denial under Medicare Part D.

Transplant immunosuppressants are often used off-label because of insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.

Investigating Novice and Expert Conceptions of Genetically Modified Organisms.

The aspiration of biology education is to give students tools to apply knowledge learned in the classroom to everyday life. Genetic modification is a real-world biological concept that relies on an in-depth understanding of the molecular behavior of DNA and proteins. This study investigated undergraduate biology students' conceptions of genetically modified organisms (GMOs) when probed with real-world, molecular and cellular, and essentialist cues, and how those conceptions compared across biology expertise. We developed a novel written assessment tool and administered it to 120 non-biology majors, 154 entering biology majors, 120 advanced biology majors (ABM), and nine biology faculty. Results indicated that undergraduate biology majors rarely included molecular and cellular rationales in their initial explanations of GMOs. Despite ABM demonstrating that they have much of the biology knowledge necessary to understand genetic modification, they did not appear to apply this knowledge to explaining GMOs. Further, this study showed that all undergraduate student populations exhibited evidence of essentialist thinking while explaining GMOs, regardless of their level of biology training. Finally, our results suggest an association between scientifically accurate ideas and the application of molecular and cellular rationales, as well as an association between misconceptions and essentialist rationales.

Generic maintenance immunosuppression in solid organ transplant recipients.

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

OBJECTIVE: To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. CASE SUMMARY: The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. DISCUSSION: The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for <24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus. CONCLUSIONS: To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAs in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.

A multicenter experience with generic tacrolimus conversion.

BACKGROUND: The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. METHODS: Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. RESULTS: Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. CONCLUSIONS: These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.