Cost Effectiveness of
Extracorporeal Photopheresis
for Treatment of Steroid
Resistant Chronic GVHD
OJOC Cohort XV
HMP 542
Daniel R Couriel
Sung Won Choi
Prachi Agarwal
Veronika Stiles
Topics to be covered
Introduction
Background of Chronic GVHD
Management of Chronic GVHD
Methods
Results
Conclusions
Hematopoietic Stem Cell Transplantation
D D D
D D D
HSCT Allogeneic
R R
RL RL
Preparative
Regimen
Allogeneic hematopoietic is an effective, but toxic treatment for
hematologic malignancies, associated with a high risk of morbidity
and mortality (10->50%), restricting its use to young patients
without comorbidities
Chronic GVHD
•
Autoimmune disorder that usually occurs after “day
100” post-transplant
•
It affects about 50% allogeneic transplants and is the
main late complication
•
It is very polymorphic, and mimics different
autoimmune diseases
•
It can affect almost any organ system
•
Skin, mucosae, conjunctivae and oral mucosa are most
frequently involved. Liver, lung, GI tract, immune
system can also be affected
4
First Line Therapy for cGVHD
• Prednisone 1 mg/kg/d is standard front line, average
therapy duration is 1-3 years (Koc, Blood 2002)
• Tacrolimus in addition to steroids does not seem to
offer any advantage (Couriel, BBMT 2004 (abs))
After Steroids
•
About 50% of patients fail steroids requiring
additional therapy
•
There is no FDA-approved therapy for these
patients (steroids are not FDA approved for
GVHD either)
•
Once patients fail steroids, we need a second
line therapy that can be efficacious and at the
same time allow for steroid taper (i.e. steroidsparing)
Extracorporeal Photopheresis (ECP)
The Instrument draws blood
from the patient
Photoactivation
with UVA light
Blood is separated by centrifugation
and red blood cells are returned
UVADEX®
White blood cells are treated with
UVADEX ® and exposed to UVA light
Comparison Second Line Therapies
ECP
RITUXIMAB
IMATINIB
58%
56%
42%
Complete Response
(CR)/
Partial Response
(PR)
40/18%
24/32%
11/31%
No Response (NR)/
Stable Disease (SD)/
Progressive Disease
(PD)
42%
44%
58%
Overall Response
(OR)
Aim
•
To develop a cost-effectiveness model suitable to
demonstrate:
– (1) the current costs and effects associated with the
use of ECP and other common second-line
treatments in patients with chronic GVHD
– (2) the budget impact of introducing ECP in the
clinical management of chronic GVHD
Methods
•
The ECP Economic Model is based on a
retrospective cost-effectiveness analysis using a
decision tree to account for mid-long term
outcomes
•
Main data sources were taken from literature
review and expert opinion for both clinical and
economic parameters and reflect current
practice guidelines in the management of
cGVHD in the U.S.
Methods
•
ECP + usual care versus comparators
– Rituximab + usual care
– Imatinib + usual care
•
Patients
– Patients with cGVHD after allogeneic HSCT
•
Perspective
– Societal
Methods
•
Time horizon
– Lifetime (class project: 1 year)
•
Discount rate
– Future costs and effects: 3%
•
Input: Costs
– Pharmacologic cost
– Diagnostic and follow-up cost
•
Input: Effectiveness
– Life year (LY)
– % improvement gained
– Quality Adjusted Life Year (QALY)
Methods
•
Patients were diagnosed with chronic GVHD on
the basis of NIH consensus and were linked to
costs, effectiveness, and survival
•
Model followed the patients (complete response
[CR], partial response [PR], stable disease [SD],
& progression) until death or when the 5 years
horizon was reached
Methods
•
Model probabilities concerning the efficacy of
ECP and alternatives and the degree of severity
were obtained from literature and relevant
medical database (Couriel UM BMT Program)
•
Effectiveness was measured as quality adjusted
life years (QALYS), life-year (LY) and
improvement gained (%)
•
An annual 3% discount rate was applied to
future costs and outcomes
Results
Response to Therapy in cGVHD
Initial
Therapy
Outcomes
after initial
Response
CR
PR
NR
PD
CR
CR
CR
CR
PD
PR
PR
PR
Death
PD
NR
NR
Death
PD
PD
Death
Death
Health Care Costs
ECP
RITUXIMAB
IMATINIB
Infusion room
Infusion
N/A
Medical Assistant
Medical Assistant
N/A
Nursing
Nursing
N/A
Med/Surg Supplies
Med/Surg Supplies
N/A
Laboratory studies
Laboratory studies
N/A
ECP Kit
Drug
Drug
Societal Costs
ECP
RITUXIMAB
IMATINIB
Travel
Travel
N/A
Loss of productivity
(driver)
Supportive care
(e.g. central line)
Loss of productivity
(driver)
Supportive care
(e.g. central line)
N/A
Adverse Events
Adverse Events
N/A
catheter related, infusion related,
neutropenia, hypogammaglobulinemia,
hypokalemia
catheter related, infusion related,
neutropenia, hypogammaglobulinemia,
hypokalemia
N/A
Cost per improvement gained
Time
(1 Year)
Cost
Cost
Difference
Imp, %
ICER
QALY
($/QALY
)
ECP
$64,165
--
CR 40%
PR 18%
16244
3.95
Rituximab
$65,925
- $1,760
CR 24%
PR 32%
17580
3.75
Imatinib
$75,555
- 11,390
CR 11%
PR 31%
36323
2.07
Utilities & Disutilities
Variable
Value
Source
UTILITIES
Complete response
0.9
Lee et al 2008
Partial response
0.75
Pidala et al 2009
Stable disease
0.6
Pidala et al 2009
Progression
0.6
Pidala et al 2009
DISUTILITIES (not
included)
Anemia/Neutropenia
Hypogammaglobulinemia
Steroid-related complications
Expert opinion
Assumptions
•
Response rates were taken from nonrandomized trials---no RCTs are available
•
Patients who achieve a certain disease stage
maintain it at year 1
•
Population homogeneity
•
There is no risk of infection and associated cost
for Imt treatment
•
Willingness-to-pay threshold ≤ $50,000 (Gold et al)
Conclusions
•
After 1 year, ECP was dominant (cheaper and
more effective) compared with alternative
treatments for all parameters:

The cost per improvement gained;

The cost per life-year gained;

The cost per QALY gained
*Using currently accepted U.S. willingness-to-pay
threshold of ≤ $50,000*
ECP as a second line therapy is more cost-effective!
Limitations
•
Limited patient population
•
No “gold standard” treatment
•
No FDA-approved therapy for these patients
•
Evaluation of our conclusions should consider that
the results are influenced by the number of ECP
sessions, dosing guidelines of Rmb and Imt, and the
cost of day at the University of Michigan Hospital
•
Results are not as generalizable due to the
variations in clinical practice, causing differences in
expenditures
Limitations Continued
•
Disease is extremely complex to be handled by TreeAge
software
! Limited understanding of cGVHD pathophysiology & ECP
biologic effects!
•
Due to possibility of changing clinical effects, our simulation
model is limited to the first year of diagnosis
•
Due to the nature of the disease, the time horizon for this
study is lifetime, but for the class purposes time horizon of 1
year was used
•
Societal perspective is limited (majority of the patients are
on Social Security)
Strength
Pioneer Population-Based Cost-Effectiveness
Analysis of ECP for the treatment of cGVHD in
the U.S., using microsimulation model with the
lifetime time horizon
Future Directions
To further evaluate the role of ECP, prospective
controlled clinical trials are indicated to
document its effect on survival, immune
function, infections and relapse of underlying
disease
will eliminate some of our assumptions for this
cost-effectiveness analysis
Thank You!