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.

Everolimus Use for Intolerance or Failure of Baseline Immunosuppression in Adult Heart and Lung Transplantation.

BACKGROUND Everolimus can be utilized after heart or lung transplantation to reduce calcineurin inhibitor associated nephrotoxicity, due to cell cycle inhibitor adverse effects, and as adjunct therapy for rejection, cardiac allograft vasculopathy, and bronchiolitis obliterans syndrome. MATERIAL AND METHODS A single-center, retrospective cohort study was conducted including 51 adult heart transplant patients (n=32) and lung transplant patients (n=19) started on everolimus due to immunosuppressive therapy intolerance or failure, between 2010 and 2017. Everolimus indication, response, efficacy, and tolerability were assessed. RESULTS Everolimus was most commonly initiated due to leukopenia/neutropenia (n=17, 33%) or renal dysfunction (n=13, 25%). Leukopenia/neutropenia resolved in 76% of patients (13 out of 17 patients). Renal function (GFR) increased 7.4 mL/min from baseline to 3 months after everolimus initiation (P=0.011). The most common adverse effects were edema (n=23, 45%) and hyperlipidemia (n=25, 49%). A high discontinuation rate was observed (n=21, 41%), mostly from edema. CONCLUSIONS Everolimus might be beneficial in heart and lung transplant patients with leukopenia or neutropenia and lead to modest, short-term renal function improvement. Patient selection is crucial because adverse effects frequently lead to everolimus discontinuation.

Individualizing immunosuppression in lung transplantation.

Immunosuppression management after lung transplantation continues to evolve, with an increasing number of agents available for use in various combinations allowing for more choice and individualization of immunosuppressive therapy. Therapeutic developments have led to improved outcomes including lower acute rejection rates and improved survival. However, a one size fits all approach for any immunosuppressive strategy may not be best suited to the individual patient and ultimately patient specific factors must be considered when designing the immunosuppressive regimen. Recipient factors including age, race, co-morbidities, immunologic risk, genetic polymorphisms, concomitant and previous pharmacotherapy, and overall immunosuppression burden should be considered. There are several significant drug-drug interactions with select immunosuppressive agents utilized in lung transplant pharmacotherapy that must be considered when choosing and devising a dosing strategy for an individual immunosuppressive agent. Herein, considerations for immunosuppression management in the individual patient will be reviewed.

Prevention and Treatment of Thrombotic and Hemorrhagic Complications in Patients Supported by Continuous-Flow Left Ventricular Assist Devices.

PURPOSE OF REVIEW: The purpose of this review is to describe the current knowledge in prevention and treatment of thrombotic (pump thrombosis and ischemic stroke) and bleeding (gastrointestinal and hemorrhagic stroke) complications in patients supported by continuous-flow left ventricular assist devices (CF-LVAD). RECENT FINDINGS: Left ventricular assist devices (LVADs) are now widely used for the management of end-stage heart failure. Unfortunately, in spite of the indisputable positive impact LVADs have on patients, the frequency and severity of complications are limitations of this therapy. Stroke, pump thrombosis, and gastrointestinal bleeding are among the most serious and frequent complications in these patients. The balance between hemorrhagic and thrombotic complications in patients supported with CF-LVAD is difficult as most patients do not necessarily fit a "bleeder" or a "clotter" profile but rather move from one side to the other of the thrombotic/bleeding spectrum. Further research is necessary to better understand the risk factors and mechanisms involved in the development of these complications.

Routine prophylaxis with proton pump inhibitors and post-transplant complications in kidney transplant recipients undergoing early corticosteroid withdrawal.

Surgical stress, corticosteroids, and mycophenolate may contribute to gastrointestinal ulcers/bleeding after kidney transplantation. Prophylactic acid suppression with H2RAs or PPIs is often utilized after transplantation, although unclear if truly indicated after early corticosteroid withdrawal (CSWD). PPIs have been associated with increased risks of Clostridium difficile infection (CDI), pneumonia, and acute rejection. This retrospective cohort study investigated benefits and risks of prolonged PPI use following kidney transplantation and included 286 kidney recipients undergoing CSWD within five d of transplant who were maintained on tacrolimus and mycophenolate mofetil/sodium. Patients on PPI before transplant, H2RA before/after transplant, and/or those with pre-transplant GI complications were excluded. A total of 171 patients received PPI>30 d, mean duration 287 ± 120 d (PPI group); 115 patients were not maintained on acid suppression (No-PPI group). GI ulceration and bleeding events were rare in PPI group (1.2% and 2.3%, respectively) and not observed in No-PPI group (p = NS). The incidence of infectious or hematological complications was not significantly different between groups. The PPI group experienced more biopsy-proven acute rejection (9.4% vs. 2.6%, p = 0.03). No direct benefit was observed with PPI in reducing the incidence of GI ulcers and bleeding events in kidney transplant recipients undergoing early CSWD. Further studies are needed to investigate the association of PPI and acute rejection.

Risk evaluation and mitigation strategy programs in solid organ transplantation: the promises of information technology.

Risk evaluation and mitigation strategies (REMS) required by the Food and Drug Administration are implemented to manage known or potential risks associated with medications and to ensure ongoing safe use throughout the life of a pharmaceutical agent. Healthcare organizations have begun to adopt information technologies with clinical decision support (CDS) to ensure safe use of medications. Systems have been expanded and customized to also ensure compliance with regulatory standards. End users who are unfamiliar with particular medication use provisions are at risk of unknowingly inappropriately fulfilling specific components. Institution-specific customization of vendor-provided CDS is useful to enhance provider awareness and ensure compliance with standards. Integration of health information technology systems to fulfill REMS requirements is novel and important to ensure consistency as healthcare standards evolve.

Changes in IgG subclasses of donor specific anti-HLA antibodies following bortezomib-based therapy for antibody mediated rejection.

The predominant anti-HLA IgG subclass during antibody mediated rejection episodes is IgG1. Class I DSA IgG subclasses respond to single cycle of bortezomib-based therapy more frequently as compared to Class II DSA IgG subclasses. High titer Class II DSA IgG subclasses are less likely to respond to single cycle bortezomib-based therapy. Future studies are needed to determine if the response to bortezomib-based therapy is dependent on the type of DSA and/or the strength of the DSA at the time of antibody mediated rejection episode.