1. Updates in Transplant Medication and Technology
Alicia Lichvar, PharmD, MS, BCPS
University of Illinois at Chicago
Department of Pharmacy Practice and Surgery
August 18th 2018

2. Disclosures
I have no actual or potential conflict of interest in relation to this presentation

3. Learning Objectives
Discuss the current practices of transplant immunosuppression in the United States (US) for renal transplant recipients
List different medications for transplant immunosuppression
Review some of the updates for transplant medication

4. Anti-Rejection Medications: A Necessary Evil, A Force for Good

5. Immunosuppression– What’s YOUR regimen?
Tacrolimus
Cyclosporine
Belatacept
Mycophenolate
Azathioprine
Sirolimus/ Everolimus
Steroids

6. Immunosuppression Regimens– Basically Spaghetti Sauce!

7. Immunosuppression Types
Desensitization therapies (aka the “bells and whistles”)
Induction therapies (aka “clearing the field”)
Maintenance therapies (aka “tricking the body”)
Rejection therapies (aka “factory reset”)
REJECTION (if needed)
DESENSITIZATION (if needed)
TRANSPLANT TIME LINE
INDUCTION
MAINTENANCE

8. Timeline Of Immunosuppression Therapies
Tacrolimus
Mycophenolate mofetil
Rituximab (CD20)
Basiliximab (CD25)
Daclizumab (CD25)
Sirolimus
Thymoglobulin
Everolimus
Belatacept
Bortezomib
Eculizumab
XL and XR-Tacrolimus
Graft survival at 1 year
50% 80%
Azathioprine
Steroids
Cyclosporine
1950
1960
1970
1980
1990
2000
2010
2020
1954 – 1st LRT
AZA – prodrug for mercaptopurine, 1957
PRED – marketed 1955
But not until 1962 first time used together (AZA-prednisone) for non identical allo-RT
At same time, animal- antibodies against human T cells
CSA – approved 1983
OKT3 1986
Irradiation
Anti-T Cell
Antibodies
Atgam
Muromonab (CD3)
Alefacept
Tofacitinib
Alemtuzumab (CD52)
Mycophenolate sodium
Graft survival at 1 year
0%  30%
Graft survival at 1 year
80%  90%

9. Immunosuppression– the Real Heroes!
Backbone agent
Adjunctive agent
Steroids (maybe)
Prevent rejection

10. Immunosuppression– the Real Heroes!
Tacrolimus and cyclosporine
Mycophenolate
Backbone agent
Adjunctive agent
Steroids (maybe)
Prevent rejection
Sirolimus and everolimus
Azathioprine
Prednisone
Belatacept
Sirolimus and everolimus

11. Maintenance IMS Toxicities
GI toxicity
Anemia
Leukopenia
MPA
Nephrotoxicity
Neurotoxicity
Hypertension
Diabetes
Hyperlipidemia
Electrolyte disorders
Hirsutism/Alopecia
GI toxicity
Gout
CNIs
Remember, immunosuppression works best when used in combination!
Edema
Anemia
Hyperlipidemia
Proteinuria
Mouth ulcers
Wound healing
mTORi
Osteoporosis
Diabetes
Weight gain
Body changes
Glaucoma
Wound healing
Steroids
PTLD
Infusion reactions
Bela

12. Seeking The Perfect Balance
Toxicity
Infection & Malignancy
Rejection

13. Which Combination is Best?
Best IMS regimen is unknown
253 Transplant Centers in USA
Every center has its own “best” protocol
Less medications vs. less of each medication?
Azathiprine + Predinsone
Sirolimus + Mycophenolate + Prednisone
Tacrolimus + Azathioprine + Prednisone
Cyclosporine + Mycophenolate + Prednisone
Tacrolimus + mycophenolate + Prednisone
Sirolimus + Tacrolimus + Prednisone
Cyclosporine + Mycophenolate
Tacrolimus + Mycophenolate
Less rejection compared to years ago
More infection?
Long term benefit?

14. Optimizing Immunosuppression
Individualization of the drug regimen to the patient
Things to think about….
Risk of rejection
Expected or existing drug side effects
Medication adherence
Other chronic illnesses (i.e. high blood pressure, diabetes mellitus)
Risk of infections

15. Optimizing Our Current Medications
“Drugs don’t work in patients who don’t take them”
- C. Everett Koop, MD
ADHERENCE to medication regimen is more crucial then ever before
At least 23% of transplant recipients don’t take their medications as prescribed

16. Defining Medication Non-adherence
World Health Organization Classification of Risk Factors for Non-adherence
Socioeconomic
Age, gender, employment status, financial status, level of education
Patient/ disease-related factors
Health beliefs/ behaviors
Treatment-related factors
Patient symptoms, side effects of medications
Healthcare system factors
Lack of health insurance or health benefits
Clin J Am Soc Nephrol 2010: 5; 1305–1311.

17. Things Patient’s Think about When They Think about Their (Transplant) Medicines
Empowerment
Fear of consequences
Managing regimen demands
Overmedicalizing life
Social accountability and motivation
Am J Transplant. 2018;18:564–573.

18. Strategies to improve adherence
Ways we can help…..
Strategies to improve adherence
Develop system of reminder cures
Involve family members and/or friends as support system
Simplify immunosuppression medication regimen (as much as possible)
Work to improve adherence when daily routines are upset
Education regarding the value and necessity of anti-rejection medicines and what to do when issues arrise
Clin Transplant 2012: 26: 706–713

19. What ways help you remember your medications?

20. Traditional Strategies
Pillboxes
Keeping medications in key locations in the house
Traveling with medications– even if you’re gone for the afternoon!
Phone alarms

21. Apps Medisafe Mango Health Round Health
Care4Today
CareZone
MedPal
MyMeds
Mango Health
Round Health
JMIR 2017;5(4):e45

22. Medisafe

23. Medisafe Comprehensive medication adherence tracker
Measurement tracker
Weight and waist circumference
A1c and blood glucose
Serum creatinine and eGFR (kidney numbers)
Blood pressure
And much more…..
Option to add in your doctors and appointment reminders

24. Medisafe
Am Heart J. 2017 Apr;186:40-47.

25. Mango Health

26. Mango Health Enter and track medications with alerts
Health habit trackers
Weight
Food recording (not as good as other apps, but available)
Blood pressure
Blood sugar
Mood

27. Mango Health

28. Round Health

29. Round Health Medication and adherence tracking
Sets a window to take medications that increase in notification intensity
With a user account, can export and synch between devices
Simple, easy, and limited to medication tracking

30. Other Non-medicine Apps
MyFitnessPal
Track steps, exercise, and other activities
Record food intake and hydration
Trend weight and body measurements
Apple Health
Tracks steps (with an Apple phone or watch)
Record medication lists (not adherence)
Document vital signs and lab values

31. Our Current Practice at UI Health: Paper!

32. Other Services We Utilize
Medication Therapy Management (MTM) Clinic
Pharmacist run clinic
Spend dedicated time with select transplant patients
Provide additional education, fill pillboxes, and help manage refills
Medication Assistance Program
Part of the UI Health Wood Street Pharmacy
Help patients in financial need obtain medication vouchers and other forms of patient assistance

33. Our Approach: Attack from all sides
Re-establishing a new routine
Medication adherence
Financial assistance
Patient and family education
Support system of doctors, nurses, social workers, and pharmacists

34. Conclusions and Final Thoughts

35. Conclusions
Much of the current literature being investigated in transplant relates to medication adherence
Adherence to medication is an important factor for transplants to maximize their lifespan and to avoid complications
The best approach to optimize medication adherence with teaming up with your healthcare team to find a customized strategy that works for you!

36. Updates in Transplant Medication
Alicia Lichvar, PharmD, MS, BCPS
University of Illinois at Chicago
Department of Pharmacy Practice and Surgery
April 14th 2018