Once patients receive their new organs, the specialty pharmacy can help them navigate through lifelong, complex transplant therapy. Here's a look at one such program.
Meeting the needs of solid organ transplant patients has long been a cornerstone of specialty pharmacy practice. Specialty pharmacies are ideally suited to help patients with this lifelong therapy that can be complex and may have negative side effects. Failure to support transplant patients with a comprehensive program to address adherence and persistency could potentially lead to rejection and possibly even failure of the transplanted organ. ModernHEALTH, a specialty pharmacy company operating out of Los Angeles, California, provides a fully integrated suite of specialty pharmacy and infusion services and offers a comprehensive patient care program to meet the complex needs of a patient who has received a transplant. This article will provide background in transplant therapy and review ModernHEALTH’s transplant program.
OVERVIEW OF TRANSPLANT MAINTENANCE THERAPY
Although preferred drug regimens may vary according to the organ that has been transplanted and by institution, the basic backbones of maintenance immunosuppression are much the same. Doses are carefully monitored and are typically high for the first few weeks after transplant, but can be decreased to a smaller dose for long-term maintenance. If rejection occurs, physicians may increase the dose of the immunosuppressant or add additional immunosuppression to the regimen.1
Immunosuppression is a careful balance between suppressing the immune response so that the graft does not reject and avoiding the risk of serious infections because of the very immuno-suppression that is protecting the transplanted organ. Immunosuppression has progressed a great deal in the 50-year history of transplantation—from regimens dominated by azathioprine and prednisone in the first 20 years of transplant, to the introduction of cyclosporine in the 1980s and mycophenolate mofetil and tacrolimus in the 1990s, to belatacept just this year.2
Although steroid-free protocols have emerged in recent years due to toxicity of long-term steroid exposure, prednisone often still plays a role in immunosuppression. Corticosteroids prevent interleukin-1 and interleukin-6 production by macrophages and prevent activation of T-cells. However, the development of side effects such as Cushing’s disease, osteoporosis, glucose intolerance, and other serious adverse events is a concern.2
Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus are used frequently in immunosuppressive regimens. They act to block T-cell transcription activities and therefore inhibit T-cell proliferation and activation. Cyclosporine is usually given with prednisone so that lower doses can be used. Cyclosporine requires periodic blood level monitoring to ensure adequate immunosuppression.
Of particular concern is cyclosporine’s propensity to cause nephrotoxicity. For this reason, it is used primarily in heart and lung transplants. Cyclosporine can cause other adverse events such as glucose intolerance and hypertension. Patients can also experience thickening of the gums and hirsutism.1
Tacrolimus exhibits the same glucose intolerance concerns but causes less gum hypertrophy and hirsutism. More than 50% of patients with new transplants are started on tacrolimus, and it is the most common drug for patients receiving a kidney, liver, pancreas, or small bowel transplant.2
Interactions with drugs that affect cytochrome P450 are a concern with both cyclosporine and tacrolimus.
Mycophenolate mofetil, mycophenolate sodium, and azathioprine are all purine metabolism inhibitors. Mycophenolate mofetil and the entericcoated mycophenolate sodium are both metabolized to mycophenolic acid (MCA). MCA inhibits both B and T cell proliferation. Some studies have shown that the enteric-coated mycophenolate sodium may cause fewer GI adverse events, but both agents can cause nausea, vomiting, and diarrhea. Azathioprine decreases RNA and DNA synthesis and can cause leukopenia, thrombocytopenia, and hepatitis. Azathioprine and mycophenolate products should not be used concomitantly.1,2
The rapamycin compounds, such as sirolimus and everolimus, are macrolides that bind to an important kinase in the cell cycle known as mammalian target of rapamycin (mTOR). Blocking mTOR is thought to suppress the G1 to S phase of the cell cycle and therefore inhibit lymphocyte proliferation. Therapeutic blood level monitoring is recommended for both sirolimus and everolimus and monitoring should occur for potential interactions with drugs that are metabolized by the cytochrome P450 system. Peripheral edema, hypertension, and hyperlipidemia are common side effects seen with these agents.
Belatacept is the newest medication to join the transplant immunosuppresion arsenal, with FDA approval on June 15, 2011. It a selective T-cell costimulation blocker and should be used only in patients who are EBV seropositive. Belatacept is administered as an IV infusion every 4 weeks during the maintenance phase.3
It was approved with a REMS program including a medication guide and a communication plan entailing a Webinar, a Dear Healthcare Provider letter, a Healthcare Provider Fact Sheet, an Infusion Specialist letter, a Pre-Infusion checklist, and journal information pieces.4
An ongoing evaluation of the belatacept safety profile has also been established through the ENLiST patient registry program.5
CURRENT ISSUES IN TRANSPLANT THERAPY
An area in which specialty pharmacists can also play an important role is the use of intravenous immunoglobulin (IVIG) for patients awaiting transplant. Patients who are highly sensitized and have high levels of anti-HLA antibodies have very low transplant rates due to the increased rejection risk these patients face.
It has been found that a protocol of high-dose IVIG therapy can reduce allosensitization, decrease acute rejection episodes, and lead to a higher success rate for highly sensitized cardiac and renal transplant patients. Many protocols are in use across the United States, but a commonly used regimen is 1 to 2 grams of IVIG per kilogram per dose given 4 times monthly. Much discussion about the cost-effectiveness of this approach has occurred; however, the cost of maintaining a patient on dialysis seems to be much greater than the IVIG treatment plus transplantation costs that have been published in available studies.6
Other protocols for highly sensitized patients utilize rituximab, an anti-CD20 antibody that reduces B-cell and antibody levels, in conjunction with IVIG. This approach is thought to decrease time to desensitization and calls for 2 doses of 2 gm/kg IVIG given 30 days apart in conjunction with rituximab 1 gram given on day 7 and day 22 of the protocol.7
Another issue in transplant therapy surrounds approved generics for immunosuppressants. Generic versions are currently available for cyclosporine, mycophenolate mofetil, and tacrolimus. However, many health care providers have been reluctant or unwilling to switch from the branded version of a product to a generic, citing narrow therapeutic indices for immunosuppressants and the risk of potential implications if a reduction in immunosuppressive levels should lead to a severe acute rejection.
Few payers seem to be aggressively managing this category at this point due to clinical sensitivity and the lack of long-term follow-up studies to determine the risk of acute rejection after a switch to generic.8
The willingness of a provider to switch from a branded version of a transplant drug to a generic varies widely by region across the country. It can even vary among transplant centers, with some providers being early adopters of the switch to generics and some providers taking a more cautious approach.
MODERNHEALTH'S TRANSPLANT PROGRAM
More than 140,000 solid organ transplants have been performed in the United States in the last 5 years.9
Once a patient receives their new organ, they can benefit greatly from the assistance of a specialty pharmacy in helping them to navigate through lifelong complex transplant therapy. ModernHEALTH is one such specialty pharmacy that provides a personalized care program tailored to the specific needs of both a transplant center and the recipients. ModernHEALTH’s program includes a spectrum of services ranging from preto post-transplant therapy management for both oral and infused medications. This focused approach and continuity of care throughout the transplant experience benefits both the patient and the transplant center team.
ModernHEALTH has more than 35 years of experience in specialty pharmacy and focuses its expertise on providing health care professionals at transplant centers and patients with outstanding customer service. ModernHEALTH’s dedicated transplant team is focused on providing customized transplant services based on the preferences of the various transplant centers that the company services by simplifying the medication ordering and discharge planning process. The goal is to ensure that the patients are receiving seamless, quality care and that the transplant centers are provided with solutions they need to remove administrative barriers so that the transplant team can focus on patient care.
ModernHEALTH understands the intricacies involved with a transplant patient’s complex and lifelong medication regimen and believes that constant communication with the patient and the transplant team is integral to long-term success. The program begins with a robust benefits verification to ensure that medications are billed appropriately and coordination of benefits is set up appropriately for the patient. Manufacturer-sponsored commercial copayment programs, manufacturersponsored patient assistance programs, and non-profit patient assistance foundations are also accessed to remove any potential financial barriers to adherence and persistency. The transplant team closely monitors dosages, side effects, and potential interactions with each medication order. In addition, particular care is given to ensuring that patients who have been switched from a branded version of an immunosuppressant to a generic version have one consistent generic manufacturer to minimize any potential problems with constant switching among manufacturers.
Adherence and persistency on transplant therapy is of the utmost importance to the ModernHEALTH team. A “Care Call” is placed to the patient when they arrive home from the transplant center to review their medications, address any questions they may have, and ensure that the patient understands and can adhere to the medication regimen, as well as to perform a baseline assessment. ModernHEALTH then enrolls the patient in a refill management program designed to contact the patient prior to the time the next refill is needed, to assess and provide tips on adherence, as well as to ensure that the correct refills are delivered in a timely manner.
ModernHEALTH has developed a customized Transplant Kit to empower each patient to monitor for potential side effects of immunosuppressant therapy and to take control of their medication adherence. The kit includes a tote bag, a blood pressure monitor, a medication organizer to aid in adherence to the medication regimen, a digital thermometer, and a pill splitter to assist the patient in receiving a more accurate dose if he or she is using half tablets. This kit is provided to the patients at discharge from the hospital and further reinforces pharmacist and transplant team education and teaching.
TRANSPLANT DESENSITIZATION PROGRAM AND HOME INFUSION SUPPORT
In addition to supporting patients with their maintenance immunosuppressant therapy after they have received their transplant, ModernHEALTH provides comprehensive support for home infusions that may be required for pre-transplant desensitization or post-transplant rejection treatment. ModernHEALTH has clinical and operational expertise in obtaining authorization, billing to the patient’s insurance, administering the infusion, and performing lab draws for a wide range of protocols. The transplant desensitization program offers infusion support and expertise for many clinical protocols, including high-dose IVIG therapy as well as protocols utilizing rituximab in conjunction with IVIG therapy. ModernHEALTH can also administer inotropes and infused antibiotics in the home and works with the transplant centers to ensure that there are no communication gaps.
COLLABORATIONS FOR SUCCESS
In order to provide outstanding care to patients and providers and to recognize additional savings and services that positively impact patient care, ModernHEALTH has chosen to work with collaborative partners such as pharmaceutical and biologic manufacturers, highly skilled nurses and pharmacists, and Managed Health Care Associates, Inc (MHA), including MHA’s Specialty Pharmacy Solutions.
MHA is a leading health care services company that offers a wide spectrum of services and solutions to support the diverse and complex needs of alternate site and specialty pharmacy providers such as ModernHEALTH. MHA provides ModernHEALTH and other member pharmacies with a comprehensive portfolio of purchasing services for both pharmaceutical products and business solutions. MHA also offers contract management and business development opportunities to member pharmacies. In support of ModernHEALTH’s transplant and immunoglobulin business, MHA works with manufacturers and distributors to maintain a diverse contract portfolio of transplant medications and immune globulins and continually works to secure product access for members. MHA’s Specialty Pharmacy Solutions program provides consistent tracking and analysis of trends in the specialty industry and MHA’s clinical services team also supports ModernHEALTH with clinical information to enhance disease state and specialty product knowledge.
LOOKING TOWARD THE FUTURE
ModernHEALTH recognizes that transplant patients need a comprehensive health care team to optimize their immunosuppressive therapy. The company has made a number of investments in their transplant program to be able to provide such resources to both the transplant center team and patients. ModernHEALTH’s investment in reporting and technology allows them to provide limited distribution products and assist manufacturers with their reporting needs with the use of advanced information systems that support data collection and reporting requirements necessary to dispense particular products. ModernHEALTH is a privately held independent organization that provides hands-on care from a specially trained therapy team, has experience with high-intensity therapies, and maintains high levels of patient and physician interaction. It provides the infrastructure necessary for the highest level of patient care and a transplant program focused on helping patients adhere to their prescribed course of therapy. ModernHEALTH also recognizes that advancing the dedicated transplant pharmacy team’s education can make a positive impact in patient care and supports involvement in the International Transplant Nurses Society (ITNS), the International Society for Heart and Lung Transplant (ISHLT), and the National Association of Transplant Coordinators Organization (NATCO). Through these investments and continual improvement of ModernHEALTH’s transplant program, they are able to best meet the diverse needs of transplant patients and transplant centers.
1. Hertl M, Markmann JF, Russell PS, Yeh H. Overview of transplantation. Merck Manual. www.merckmanuals.com/professional/immunology_allergic_disorders/transplantation/overview_of_transplantation.html?qt=transplantation&alt=sh
. Published 2008. Accessed September 29, 2011.
2. Pellegrino M, Schmidt, RJ, Shapiro, R et al. Immunosuppression. MedscapeReference website. http://emedicine.medscape.com/article/432316-overview#showall
. Published May 24, 2011. Accessed September 29, 2011.
3. Nulojix prescribing information. BMS. http://packageinserts.bms.com/pi/pi_nulojix.pdf. Published June 2011
. Accessed September 29, 2011.
4. Nulojix REMS. FDA website. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM261934.pdf. Published June 2011. Accessed September 29, 2011
5. Risk evaluation and mitigation strategy. BMS. http://www.nulojix.com/hcp/rems.aspx. Published June 2011. Accessed September 29, 2011
6. Jordan SC, Voa AA, Peng A, Toyoda M, Tyan D. Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Am J Transplant
. 2006;6(3):459-466. www.medscape.com/viewarticle/523523_print
. Accessed September 29, 2011.
7. Vo A, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med.
. Accessed October 21, 2011.
8. Switching transplant patients from Prograf to generic drug offers array of challenges. Specialty Pharmacy News, October 2011. Volume 8, Number 10.
9. Transplants in the US by State, 2009 and 2010. US Department of Health and Human Services, Health Resource and Services Administration, and Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov/latestData/rptData.asp
. Accessed October 13, 2011.
The above information is a selective summary of publicly available information and is accurate as of the date of writing. Please consult the sources for complete reference information. The views expressed in this article are those of the authors alone and not of Managed Health Care Associates, Inc or ModernHEALTH. Any patient care, treatment, dosing, or other decisions related to the subject matter of this article should be based on an independent evaluation of the patient’s condition and medical history by his/her treating physician.
About the Authors
Theresa Wokuluk has worked in both the specialty pharmacy and infusion industries in multiple disease states, with specialized experience in transplant and a background in pharmaceutical sales. Her goal is to ensure that patients and referral sources receive exceptional customer care. She has been involved with the transplant community on a national level since 2005 and is currently the director of transplant services at ModernHEALTH, a specialty pharmacy and infusion organization based in Monrovia, California.
Stacey Ness, PharmD, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence and persistency programs, and chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is currently associate director of specialty services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.