Optimal Timing of Hepatitis C Treatment for Patients on the - PowerPoint Presentation

Slide1

Optimal Timing of Hepatitis C Treatment for Patients on the Liver Transplant Waiting List

Jagpreet Chhatwal

,

PhD,

1,2

Sumeyye Samur, PhD

1,2

Brian

Kues

, MS,

3

Turgay

Ayer, PhD,

3

Mark S. Roberts, MD, MPP,

3

Fasiha Kanwal, MD, MSHS,

5,6

Chin

Hur

, MD,

1,2

Drew MS Donnell,

3,4

Raymond T. Chung, MD

1,2

1

Massachusetts General Hospital, Boston,

MA,

2

Harvard

Medical School, Boston, MA

3

Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA

USA,

3

Department

of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA,

USA,

4

Department

of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA,

USA,

5

Department

of Medicine, Baylor College of Medicine, Houston, TX

USA,

6

Houston

Veterans Affairs Health Services Research and Development Center of Excellence, Michael E.

DeBakey

Veterans Affairs Medical CenterSlide2

Consulting: Complete HEOR Solutions; Gilead; Merck & Co., Inc.

Grant/Research Support

: NIH/National Center for Advancing Translational Sciences

© 2016 AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES WWW.AASLD.ORG

2

Jagpreet Chhatwal

I disclose the following financial relationship(s) with a commercial interest:Slide3

Benefits of Oral DAAs for Liver Transplant CandidatesT

he availability of oral DAAs has altered the treatment paradigm for both pre- and post-LT patients

Treatment is now feasible with high success

rates

I

mprovements

in MELD scoreReduced rate of HCV recurrence post LT and need for re-transplantationSVR  fibrosis stabilization or regression and improved graft survival3Slide4

Treat HCV pre- or post-LT?

Pros of Pre-LT Treatment

Pre-LT treatment of HCV can improve patients’ MELD score and improve survival on the wait

list

Waiting until the LT

could

result in worsening of the underlying liver condition and increase the likelihood of mortality on the waiting list Cons of Pre-LT TreatmentPre-LT treatment could delay patients’ liver transplant by moving them further down the waiting listBy improving MELD score by a few points, some patients could also fall below the range for liver transplantation without obviating the need for liver transplant“MELD limbo” or “MELD purgatory” 4Slide5

Dilemma: Optimal Timing of HCV Treatment

5Slide6

ObjectiveTo identify LT-eligible patients with decompensated cirrhosis who will

benefit (and not benefit) from pre-LT treatment based on their MELD

scores

6Slide7

ApproachIdeally, a

randomized controlled trial could inform the optimal timing of HCV treatment

However, such a trial will be prohibitively large and time consumingIn such situations, mathematical modeling can inform optimal

strategies

We simulated a

virtual trial

comparing long-term outcomes of pre- versus post-LT HCV treatment with oral DAAs for patients having MELD scores between 10 and 40We developed a Markov-based microsimulation model that simulated the life course of patientsSIM-LT (Simulation of Liver Transplant Candidates)7Slide8

Pre-LT Disease progression

Efficacy of HCV Treatment

Changes in MELD Scores

Likelihood of Liver Transplant

SIM-LT Model

Post-LT Disease Progression

Quality of Life

HCV Treatment Pre- vs Post-LT

Life years for each MELD score

QALYs for each MELD score

Outcomes by UNOS region

1

-year and 5-year transplant survival (validation)

Changes in Transplant Waiting List

Outcomes

SIM-LT

(

S

imulation

of

Liver

T

ransplant

C

andidates

)

Patient demographics

5Slide9

Simulation of Timing of HCV Treatment

9

F3–F4

SVR

Liver-related Death

Graft Failure

Antiviral Treatment

Waiting List

Post-LT Treatment

No SVR

All-cause Death

Waiting List

INPUTS

OUTPUTS

Life years

QALYs

1-year & 5-year patient

survival

Patient characteristics

Mortality rates

Transition probabilities

Quality of

life

Treatment efficacy

HCV+

Validated with OPTN data

HCV-

Pre-LT Treatment

F0–F2

Liver Transplant

 Slide10

Model InputsPatient characteristics

Decompensated cirrhosis having MELD scores in the range of 10–40

mean age: 50HCV genotypes 1 or 4

Treatment efficacy

SOLAR 1 and SOLAR 2 (sofosbuvir and ledipasvir)

Likelihood of liver transplant

Massie et al. 2011Considered reduced likelihood of LT due to loss of access to HCV+ donor organs10Massie AB, et al. MELD Exceptions and Rates of Waiting List Outcomes. Am J Transplant 2011;11:2362-2371.Slide11

Inputs: MELD Score Change

11

Gane et al., AASLD 2015 Abstract 1049

MELD score change on the LT waiting list

UNOS data

MELD score change after achieving SVR

SOLAR 1 and SOLAR 2Slide12

Model Results

12Slide13

Model Validation: Patient Survival13Slide14

Life Expectancy: Pre-LT vs Post-LT14Slide15

HCV Treatment Pre- OR Post-LT?15

Difference in life years if HCV is treated

pre

-LT versus

post

-LT

Pre-LT Treatment Improves Life ExpectancySlide16

HCV Treatment Pre- OR Post-LT?16

Difference in

QALYs

if HCV is treated

pre

-LT versus

post-LTPre-LT Treatment Improves QALYs Slide17

Variations in Results by UNOS Regions:UNOS Region 3

17

Pre-LT Treatment Improves Life ExpectancySlide18

HCV Treatment Pre- OR Post-LT?UNOS Region 9

18

Pre-LT Treatment Improves

Life ExpectancySlide19

Comparison by UNOS Region19Slide20

LimitationsWhile the guidance offered by this model is useful,

recommendations may still need to be individualized for special situationsFor example, our

results may not apply where patients’ urgency for LT is not determined by MELD score Our analysis did not consider patients with HCC

We did

not explicitly model Child

Turcotte

-Pugh class in our analysisWe did not model patient dropout from the waiting list resulting from MELD improvement20Slide21

ConclusionsWe conducted a comprehensive analysis of the tradeoffs of HCV treatment pre- versus post- liver transplant

Optimal MELD score threshold

below which to treat HCV in patients on the transplant waiting list is between MELD scores 23–27, depending on the UNOS

region

Our

results may help inform clinicians about the timing of HCV treatment in liver transplant

candidates 21Slide22

Optimal Timing of Hepatitis C Treatment for Patients on the Liver Transplant Waiting List

Jagpreet Chhatwal

,

PhD,

1,2

Sumeyye Samur, PhD

1,2 Brian Kues, MS,3 Turgay Ayer, PhD,3 Mark S. Roberts, MD, MPP,3 Fasiha Kanwal, MD, MSHS,5,6 Chin Hur, MD,1,2 Drew MS Donnell,3,4 Raymond T. Chung, MD1,2 1Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA3Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA USA, 3Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA, 4Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA, 5Department of Medicine, Baylor College of Medicine, Houston, TX USA, 6Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center