Nucleoside Reverse Transcriptase Inhibitors without HBIG Can Be Safely and Cost-Effectively Administered To

Prevent Recurrent Hepatitis B Viremia Post-Liver Transplant

E. Grodstein, B. Gelb, R. Layman, R. Mittal, L. Teperman

June - 2013Sidney, Australia

DISCLOSURE

The author has nothing to disclose

Randomized trial of emtricitabine/tenofovir disoproxil

fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation – Liver Transplantation 19

Lewis W. Teperman Fred Poordad Natalie Bzowej Paul Martin Surakit Pungpapong Thomas Schiano John Flaherty Phillip Dinh Stephen

Rossi G. Mani Subramanian James Spivey - DOI: 10.1002/lt.23628

3

BACKGROUND

BackgroundHBIG prophylaxis is routinely prescribed to

prevent HBV recurrence post-OLT

HBIG prevents recurrence by neutralizing HBsAg

Long-term prophylaxis with HBIG is inconvenient and expensive, but is the mainstay of post-transplant therapy.

Cost of HBIG Based on Dosing and Administration Strategy

Yearly cost of different schedules of HBIg administration in Euros. The “on demand” schedule using 2,000 IU of HBIg allows a savings of over 50% compared with fixed monthly doses of 5,000 IU.

Di Paolo et al. Transplantation 2004; 77: 1203-1208.

Study Design

FTC + TDF is given as a fixed-dose combination tablet (Truvada) taken once daily

FTC/TDF+HBIG

Week 24

Year 2

Week 96

FTC/TDF

FTC/TDF+HBIGN=40

• OLT recipientforCHB infection

• 12 weeks ofprophylactic therapyincluding HBIG

•HBV DNA negative

•HBsAg negative

Enrollment

RANDOMIZATION 1:1

Patient DispositionScreened

N=51

EnrolledN=40

Week 24N=37

FTC/TDF+HBIN=19

FTC/TDFN=18

Completed Week 96 N=16

Discontinued N=2N=1

N=51

N=40

Randomized Week 24N=37

Discontinued N=3

GN=19 N=18

Completed Week 96 N=18

Discontinued

Creatinine Clearance Over Time

9<50 N= 9 9 9 9 9 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 2450-80 N= 24 24 24 24 24 24 24 24 24 24 24 22 22 22 22 22 22 22 22 21 21 7>80 N= 7 7 7 7 7 6 6 6 6 6 6 5 5 5 5 5 5 5 5 5 5

Virologic Outcomes All patients maintained HBV DNA below

LLOQ (Roche COBAS TaqMan assay; LLOQ=169 copies/mL) during the study period

No evidence of HBV recurrence All subjects remained HBsAg negative No re-initiation of HBIG No evidence of resistance to FTC/TDF

Conclusions

No patient on FTC/TDF who discontinued HBIG had detectable HBV DNA or HBsAg

FTC/TDF is well tolerated in post-OLT patients

Creatinine clearance remained stable and managed with labeled dose reductions

These data support the use of FTC/TDF without HBIG for the prevention of post-OLT HBV

AIM

Demonstrate the cost-effectiveness

of such therapy based on current

medication, nursing and infusion center costs.

METHODS• Retrospective chart review of 62 patients (75.8%

male, average age 59 years old) post-OLT for HBV-related disease at large urban transplant center

• Patients treated with at a minimum 6 months HBIG+TDF/E at which point HBIG was discontinued and transition solely to oral TDF/E monotherapy

• Cohort analyzed to identify patients who became HBV DNA positive (threshold of 1.6log IU, lower limit of detection by PCR)

• Time of monotherapy treatment is calculated as time from last HBIG infusion to last negative HBV DNA level

• Cumulative cost of HBIG infusions calculated (assuming 10,000IU every 2 months, the average in the first 6 month period) for the period that patients were on TDF/E monotherapy; this yielded the medication related cost savings.

• Annual Cost savings are calculated by dividing medication related cost savings by median time of TDF/E monotherapy

Department of Transplant Surgery

Percent Male Average Age Percent w/ HCC0

10

20

30

40

50

60

70

80

90

100

Patient Characteristics

0 200 400 600 800 100012001400160018000

50000

100000

150000

200000

250000

Medication Cost Difference Over Time

TDF/E Monother...

Days Since Last HBIG

Cost

($

)

RESULTS• One patient developed HBV viremia

while receiving oral TDF/E monotherapy, a 98.4% treatment success rate. This patient was concurrently receiving chemotherapy for metastatic hepatocellular carcinoma.

• Median seronegative interval on TDF/E monotherapy 86 wks (range 2-228 wks)

• Cost savings compared with conventional HBIG-based therapy:

• $49,804/patient over study• $28,150/patient life year

• Our center’s 10 year patient survival for liver transplantation for HBV-related disease is currently nearly 75%

• Significant cost savings (>$250,000 per patient) may be realized over a recipient’s life span

CONCLUSIONS• After at least 6 months of TDF/E+HBIG post-OLT, TDF/E

monotherapy can be utilized for prevention of HBV recurrence with minimal risk and high cost savings.

• Maintenance on TDF/E monotherapy is easy, well tolerated.

• Discontinuation of HBIG monthly infusion significantly impacts the time and staffing necessary to maintain patient compliance.

• Cost savings of approximately $28,000 per patient per year of therapy are realized in HBIG discontinuation alone.