Positioning Specialty Pharmacy to Care for Solid Organ Transplant Recipients

The distribution of oral immunosuppression across the country following a solid organ transplant is complex and not frequently described throughout current literature. This is partly because there is not a straightforward process for health-systems, pharmacies, or patients.

Furthermore, very few people are in a role to understand the fickle dynamics from the business of pharmaceuticals to the clinical application of transplant patient care. Variable factors influencing the process include provider medication preferences, location of transplant centers (different laws by state, Medicaid eligibility, etc.), location of pharmacies (community versus mail-order), formulary restrictions per the patient’s insurance, co-pays, patient assistance program qualifications, and discount cards.

Although these dynamics are not all unique to solid organ transplant, they are brought to light more dramatically due to the sudden nature of organ availability and criticality of immunosuppressing agents. Before patients are approved by a medical center to be listed for organ transplantation, they must undergo a rigorous process of evaluation. The thorough assessment by physicians, surgeons, pharmacists, case managers, and others also typically includes a review of the patient’s financial ability and insurance coverage for transplant.

It is important and responsible for patients and transplant programs to understand financial liabilities prior to performing a major procedure that has lifelong implications. However, depending on the organ(s) a patient is listed for and a multitude of other factors, some patients may wait a duration of 2 days to 5 years on the transplant list.

During this time, it is possible for insurance coverage or the specifics of coverage (i.e., co-pays) to change. This, unfortunately, is why many patients do not know how much their transplant medications will cost or from where they will be able to obtain them (i.e., community pharmacy, specialty pharmacy, or mail order requirements) until the organ transplant has been completed and the insurance company is billed for new prescriptions.

The challenge of expensive co-pays or mail order restrictions can be overcome during the index hospitalization with free trial cards or 1-time overrides, for example; however, future refills become an issue a month later and potentially every year that the insurance coverage changes. Although many specialty and/or transplant trained-pharmacists have become accustomed to these nuances and have developed practices to maneuver them, the process is not straightforward for clinicians nor patients long-term.

So why do all insurances have different coverages of immunosuppressant drugs when patients need them to survive? Why are some patients mandated to fill them at specialty pharmacies and others are not?

The former question is more complex, but the latter has a history that can be described more clearly. The success of immunosuppression for long-term viability of transplanted organs in humans dates back to the use of steroids and azathioprine in the 1960s.¹

As medical science progressed, calcineurin inhibitors (i.e., cyclosporine and tacrolimus) were found to benefit patient and graft survival in the late 1980s to early 90s with the eventual discovery of mycophenolate in the mid- to late-1990s.^1,2

The triple-drug regimen of tacrolimus, mycophenolate, and prednisone are now the most utilized medications across all types of solid organ transplant. In 2016, the estimated cost of medications per patient per month, depending on the various factors mentioned previously, was upwards of $2500 per month.³

During the time that kidney transplantation was becoming available in the 1970s to those suffering from end-stage renal disease, legislative activity ensued to cover the costs of dialysis and/or renal transplantation for all Americans who waited a designated amount of time.⁴ At that time, the original drugs used to maintain immunosuppression posttransplant were inexpensive, and only the few patients with a high likelihood of success posttransplant underwent surgery.

It was soon realized that dialysis was more expensive than transplant, therefore, the 1 year of coverage for transplant patients was extended to 3 years. Obtaining medication and paying for medication was no problem; however, as science progressed, patients lived longer and drugs became more expensive.

Legislation in the mid-1980s responded by covering immunosuppressive medications for 1 year after a Medicare-covered renal transplant. Eventually, patients who received a kidney transplant were surviving longer than those who stayed on dialysis and annual costs were 60% less expensive to the health care system. Therefore, Medicare coverage of immunosuppression was extended to 3 years in 1992.⁴

The longevity of a successful kidney transplant is associated with the use of cyclosporine and tacrolimus in the early 1990s, and distribution of these transplant medications is frequently described with the conception of specialty pharmacy. It was recognized that kidney transplant patients are in need of complex medication management and assistance in overcoming the hurdles of high drug costs.

For the first 3 years posttransplant, a patient’s drug costs are completely covered, but afterwards, patients must navigate acquisition of drug through private insurance or via qualification of extended Medicare coverage for long-term graft survival. Historically, it seemed as though specialty pharmacy services were in prime position to manage this for patients.

As discussed by Scott Kober in The Evolution of Specialty Pharmacy, “unlike retail stores, [specialty pharmacies were] focused more on chronic conditions with higher-than-average prescription prices”…he goes on to describe specialty pharmacy services, “as expensive lifesaving therapies became available, paperwork and treatment costs posed an issue to patients who retrieved these prescriptions from retail stores. Locations did not always have these costly drugs in stock, and most requested that patients pay for their drugs up front and complete insurance paperwork.”⁵

His examples that lead to the innovative concept describe the dire need for transplant patients to obtain medications but lacking the health literacy to complete the complicated insurance forms. Unfortunately, the same problems in accessing transplant medications still exist today, despite the fact that specialty pharmacies have continued to exist, and clinical practice has continued to improve the duration of survival following transplant.

The 3-year rule for Medicare coverage still exists today and no universal definition or requirement exists for transplant medications to be filled through a specialty pharmacy as a safety net to aid patients in their transitions of insurance. Therefore, this challenge is faced by patients who are lost to follow-up when their 3-years of Medicare expire, or their private insurance coverage changes.

This results in difficulty procuring drug and non-adherence to immunosuppression, which has been shown to be one of the leading causes of graft loss. While patients do not need a kidney transplant to survive, the costs of returning to dialysis after a failed kidney transplant thereby revert back to increasing overall health care costs.

Enter specialty pharmacy services: Dedicated pharmacies that are well-equipped and actively pursuing technology to make high-touch patient services more efficient and improve adherence to high-cost drugs. In its simplest form, a specialty pharmacy can effectively dispense, monitor, and follow-up with transplant patients who are maintained on the standard triple-drug immunosuppression regimen.

Cyclosporine and tacrolimus are narrow therapeutic index drugs with many adverse effects and are the backbone of immunosuppression. Pharmacists are well-positioned to counsel patients on these regimens, make interventions on common drug interactions, and ensure sufficient supply as doses change.

Although any pharmacist can perform these tasks, many community pharmacies do not have the same capabilities of specialty pharmacies that maintain close relationships with patients. As transplant medications and clinical science advances, new medications prescribed to patients will likely be infused and/or injected, which will increase the complexity of services required.

Immunosuppression in the pipeline is intravenous and many ancillary drugs used in the transplant population are injectable. For example, myelosuppression is associated with multiple drugs utilized posttransplant and can be treated with growth colony stimulating factors.

Many biosimilars have recently come to market that are being prescribed to transplant patients. Although biosimilars have decreased medication costs compared to their branded counterparts, they can still be cost-prohibitive to patients and require supportive instruction that a community pharmacy may not be equipped to provide.

Specialty pharmacy has progressed greatly over the past 20 years and is in prime position to aid the government and insurance companies in reducing health care costs following solid organ transplant. More research in specific application of these services needs to be completed to directly analyze which services during which phase of care provide the most cost savings, but specialty pharmacy has an exciting start.

Clinical practice in solid organ transplant is progressing, and it is in the interest of patients, clinicians, and payers to partner with specialty pharmacies to improve drug adherence, aid transition between insurance coverages, and reduce health care costs for the community.

About the Author

Mackenzie Goltz (Magid) earned her Doctor of Pharmacy degree from The University of Kansas and her Master of Pharmacy Business Administration (MPBA) degree at the University of Pittsburgh School of Pharmacy/Joseph M. Katz Graduate School of Business, a 12-month, executive-style graduate education program designed for working professionals striving to be tomorrow’s leaders in the business of medicines. Mackenzie completed a PGY1 Pharmacy Residency and PGY2 Solid Organ Transplant Pharmacy Residency at Duke University Hospital, where she currently practices as a clinical pharmacist.

References

1. Starzl TE. History of clinical transplantation. World J Surg. 2000;24(7):759-782. doi:10.1007/s002680010124
2. Shipkova M, Armstrong VW, Oellerich M, Wieland E. Mycophenolate mofetil in organ transplantation: focus on metabolism, safety and tolerability. Expert Opin Drug Metab Toxicol. 2005 Oct;1(3):505-26. doi: 10.1517/17425255.1.3.505. PMID: 16863458.
3. James A, Mannon RB. The Cost of Transplant Immunosuppressant Therapy: Is This Sustainable?. Curr Transplant Rep. 2015;2(2):113-121. doi:10.1007/s40472-015-0052-y
4. Institute of Medicine (US) Committee on Medicare Coverage Extensions; Field MJ, Lawrence RL, Zwanziger L, editors. Extending Medicare Coverage for Preventive and Other Services. Washington (DC): National Academies Press (US); 2000. APPENDIX D, PART 2, Transplantation and Immunosuppressive Medications: Evolution of Medicare Policy Involving Transplantation and Immunosuppressive Medications—Past Developments and Future Directions. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225248/
5. Kober S. The evolution of specialty pharmacy. Biotechnol Healthc. 2008;5(2):50-51.