Cost Effectiveness

Wepsięć 2012 (Poland)¹

 

Population:	Adults with steroid-refractory acute GvHD after allogeneic HSCT*
Intervention:	THERAKOS ECP ImmunomodulationTM (1-month cycle length; Cycle 1: ECP performed on 2 consecutive days every week; Cycle 2+3: procedure performed on 2 consecutive days fortnightly; Cycle 4+: performed on 2 consecutive days monthly [if required])
Cost comparator:	None, due to lack of guidelines and standard of care
CE outcomes:	CER (PLN/LY gained) over a 3-year time Horizon (CE Threshold† = 33,181 PLN/LY): Adults with acute GVHD, 24,103.30 PLN/LY
Study design:	Markov decision model constructed to analyse cost-effectiveness of ECP in adults and children with acute and chronic steroid-refractory GvHD Outcome presented as a CER of cost per life year in each group No comparator due to a lack of guidelines and standard of care Direct medical costs were assessed
Limitations:	Lack of randomised controlled trials comparing the use of ECP with current therapies Clinical trials used to build the model reported ECP efficacy results, inclusion criteria, and organ incidence differently or not at all QoL and potential AEs were not considered Mortality data was prepared based on the selected patient group of the study from which the data originated and was not combined

 

*Subgroup analysis not representative of the entire study population.

†The CE threshold is calculated as a value of GDP per capita, between 2007–2009, GDP was estimated at 33,181 PLN, a cost-effective therapy is 2 x GDP, a highly cost-effective therapy is 1 x GDP.

AE, adverse event; CE, cost-effectiveness; CER, cost-effectiveness ratio; ECP, extracorporeal photopheresis; GDP, gross domestic product; GvHD, graft-versus-host disease; HSCT, haematopoietic stem cell transplantation; LY, life-year; PLN, Polish zloty (currency of Poland); QoL, quality of life.

1. Wepsięć K, et al. Instytut Arcana; 2012. 80 p.

De Waure 2015 (Italy)¹

 

Population:	Adults with steroid-refractory acute GvHD after allogeneic HSCT*
Intervention:	THERAKOS ECP ImmunomodulationTM (month 1: 2 cycles/week for 4 weeks; month 2: 2 cycles/week every other week; from month 3 onward: 2 cycles/month)
Cost comparator:	Mycophenolate (20 mg/day) Pentostatin (1 mg/m2 for 6 days in a 3-month period) Imatinib (200 mg/day)
CE outcomes:	ICUR (€/QALY gained) over a 7-year time horizon: - Vs all three alternatives, ECP was dominant†
Study design:	Current therapeutic approaches were identified, and their efficacy and safety was assessed through a literature review and expert questionnaire Decision tree model associated with a Markov model was adapted to the Italian NHS setting and applied to a hypothetical cohort of 1,000 patients Direct medical costs were assessed
Limitations:	Patient attitudes, behaviours, and QoL were not captured Questionnaires used to assess alternative therapies and their costs were not validated Markov modelling is not a real-world simulation and the data used to populate it may not be reliable Few safety and efficacy studies for ECP alternatives available Studies were not head-to-head and had small sample sizes Utilities chosen according to one study Neutropenia was the only drug-related AE considered

 

*Sub group analysis not representative of the entire study population.

†Compared with alternatives, a treatment or intervention is dominant when it is both more effective and less costly.

AE, adverse event; CE, cost-effectiveness; ECP, extracorporeal photopheresis; GvHD, graft-versus-host disease; HSCT, haematopoietic stem cell transplantation; ICUR, incremental cost-utility ratio; NHS, National Health Service; QALY, quality-adjusted life year; QoL, quality of life.

1. de Waure C, et al. Value Health. 2015;18(4):457-466.

Wepsięć 2012 (Poland)¹

 

Population:	Adults with steroid-refractory acute GvHD after allogeneic HSCT*
Intervention:	THERAKOS ECP ImmunomodulationTM (month 1: 2 cycles/week for 4 weeks; month 2: 2 cycles/week every other week; from month 3 onward: 2 cycles/month)
Cost comparator:	Mycophenolate (20 mg/day) Pentostatin (1 mg/m2 for 6 days in a 3-month period) Imatinib (200 mg/day)
CE outcomes:	ICUR (€/QALY gained) over a 7-year time horizon: Adults with chronic GvHD, 30,473.46 PLN/LY
Study design:	Markov decision model constructed to analyse cost-effectiveness of ECP in adults and children with acute and chronic steroid-refractory GvHD Outcome presented as a CER of cost per life year in each group No comparator due to a lack of guidelines and standard of care Direct medical costs were assessed
Limitations:	Lack of randomised controlled trials comparing the use of ECP with current therapies Clinical trials used to build the model reported ECP efficacy results, inclusion criterai, and organ incidence differently or not at all QoL and potential AEs were not considered Mortality data was prepared based on the selected patient group of the study from which the data originated and was not combined

 

*Subgroup analysis not representative of the entire study population.

†The CE threshold is calculated as a value of GDP per capita, between 2007–2009, GDP was estimated at 33,181 PLN, a cost-effective therapy is 2 x GDP, a highly cost-effective therapy is 1 x GDP.

AE, adverse event; CE, cost-effectiveness; CER, cost-effectiveness ratio; ECP, extracorporeal photopheresis; GDP, gross domestic product; GvHD, graft-versus-host disease; HSCT, haematopoietic stem cell transplantation; LY, life-year; PLN, Polish zloty (currency of Poland); QoL, quality of life.

1. Wepsięć K, et al. Instytut Arcana; 2012. 80 p.

Crespo 2012 (Spain)¹

 

Population:	Adults with steroid-refractory chronic GvHD after allogeneic HSCT*
Intervention:	THERAKOS ECP ImmunomodulationTM (3 sessions/week for first 2 weeks, 1 session every 15 days until 3 months)
Cost comparator:	Rituximab Imatinib
CE outcomes:	ICER (€/QALY over a 5-year time horizon (CE threshold†= €30,000/QALY) €24,442/QALY
Study design:	Microsimulation model of clinical characteristics based on published reports adjusted according to clinical opinion Up to 1,000 hypothetical patients were randomly generated and entered into the model Treatment efficacy, organ involvement and survival of each disease state was applied ICER was calculated as a proportion of cost and effectiveness of ECP versus comparator Direct healthcare costs were assessed
Limitations:	Theoretical mathematical model made assumptions from different sources Studies used had variable treatment protocols with treatment cycles dependent on clinical response ECP-related reduction of immunosuppressive therapies was excluded from the analysis Data were taken from small-cohort studies and case studies, not robust large-scale randomised clinical trials

 

*Subgroup analysis not representative of the entire study population.

†The CE threshold is an ICUR threshold below which an intervention is deemed cost-effective.

CE, cost-effectiveness; ECP, extracorporeal photopheresis; GvHD, graft-versus-host disease; HSCT, haematopoietic stem cell transplantation; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; QALY, quality-adjusted life year.

1. Crespo C, et al. Clin Ther. 2012;34(8):1774-1787.

Geskin 2018 (United States)¹

 

Population:	Advanced CTCL Stage 2b or higher in 70% of patients
Intervention:	ECP*
Cost comparator:	Methotrexate
CE outcomes:	ICER over a 6-month time horizon† $213,416
Study design:	Decision analytic model of systemic monotherapies for CTCL Model included variable distributions for effectiveness rates, frequency of AEs, dosing, and costs Effectiveness was measured as the overall response rate ICERs for each regimen determined relative to the lowest cost option from the payer perspective First- and second-order Monte Carlo simulations conducted to allow cost and success measurements of each regimen
Limitations:	Lack of comparable data for clinical efficacy among the treatment options Results driven by the estimated costs associated with each treatment and documented efficacy Not all possible systemic therapies were included Sequential or concomitant treatments were not considered

 

*Device used and treatment regimen were not specified within the model used.

†Cost-effectiveness threshold was not provided in the report, costs were compared to the lowest-cost-treatment methotrexate

AE, adverse event; CTCL, cutaneous T-cell lymphoma; ECP, extracorporeal photopheresis; ICER, incremental cost-effectiveness ratio.

1. Geskin, Malone DC. J Dermatolog Treat. 2018;29(5):522-530.

Peacock 2020 (Australia)¹

 

Population:	Erythrodermic (Stage T4, M0) CTCL patients (start age 64 years), refractory to first-line systemic treatment (methotrexate or interferon-α)
Intervention:	THERAKOS™ ECP (two consecutive days of treatment per month for 6 months; one treatment every 6 weeks thereafter)
Cost comparators:	Methotrexate Pegylated interferon-α Vorinostat Brentuximab vedotin
CE outcomes:	ICUR ($AUS/QALY gained) over a 5-year time horizon* vs all four alternatives, ECP was dominant†) ECP was associated with an incremental cost reduction of $21,224–122,543 and an incremental QALY gain of 0.20–0.21
Limitations:	High-grade evidence for ECP in the treatment of CTCL is limited. Utility values for psoriasis were applied as a proxy for CTCL as no quality-of-life studies were identified in the literature. There is limited to no published data available for disutility related to specific treatments for CTCL

 

*Treatment-related AE costs were not included in the model, which favoured comparator therapies given most are associated with a significant number of grade 3 or 4 AEs. However, disutilities were applied to comparator therapies calculated using the frequency and severity of AEs in published trials and existing literature.

^†Compared with alternatives, a treatment or intervention is ‘dominant’ when it is both more effective and less costly.

1. Peacock A et al - Value Health. 2020;25(6):965–974. doi:10.1016/j.jval.2021.11.1364

ECP has been shown to be cost-effective compared to other pharmacological therapies for the treatment of BOS¹

 

After the addition of ECP to standard immunosuppressive therapy:

Less need for retransplantation2 Improved survival rates2,3 Low rates of reported AEs including citrate reactions, vasovagal reactions, dyspnoea hypopotassaemia, and GI bleeds associated with low platelet counts3

 

AE, adverse event; BOS, bronchiolitis obliterans syndrome; CLAD, chronic lung allograft dysfunction; ECP, extracorporeal photopheresis; GI, gastrointestinal.

1. Zia A, et al. Value Health PRS14. 2019;22(2):S351. 2. Jaksch P, et al. J Heart Lung Transpl. 2012;38(4S). 3. Benden C, et al. J Heart Lung Transpl. 2017;36:921-933.

 

Jaksch 2012 (Austria)¹

 

Study design:	Single-centre prospective study THERAKOS ECP ImmunomodulationTM for 2 successive days (months 1-3: every 2 weeks; months 4+: every 4 weeks) FEV1 was used as a surrogate marker of response and was measured at 3,6, and 12 months after ECP
Population:	Lung transplant recipients (n=1,012) who subsequently developed BOS Stage 1 (n=194 Treated with ECP (n=51) Not treated with ECP (n=143) All patients recived standard maintenance immunosuppression
Endpoints:	Primary: Rate of change in lung function before and after the initiation of ECP Secondary: Patient survival, ECP AEs, and infectious complications
Patients treated with ECP:†	Had improved long-term survival (2,912 vs 2,422 days, p=0.046) Had lower incidence of CMV disease (0.06% vs 0.24% of patients, p=0.001) Improvement or stabilisation of FEV1 in 61% of patients treated with ECP after 3, 6, or 12 months
Outcomes in ECP group vs non-ECP:	More patients in the ECP group showed >20% loss of FEV, within 6 months (55% vs 39%, p=0.045) Less retransplantation in ECP-treated group (18 vs 21, p=0.04) Longer times to retransplantation in ECP group (1,839 vs 947 days, p=0.006)
ECP responders:	Showed improved graft survival Showed a significantly lower need for retransplantation vs non-responders (7 vs 11, p=0.001)‡
	No patients discontinued treatement and no ECP-related AEs were reported
Factors IMPROVING response to ECP:	Shorter time to BOS after transplantation(p=0.05) Lower BOS stage at the start of ECP (p=0.05)
Factors DECREASING response to ECP:	Patients with CF (p=0.007) Rapid decline in lung function at the start of BOS (p=0.048) Late BOS with rapid onset (p=0.022)
Limitations:	Small patient cohort Non-randomised (no external control group) Inclusions based on clinical ground and response to first-line BOS treatment T-cell count before and after ECP was not analysed; these cofactors could not be excluded from the cohort

 

*Triple-drug regimen of calcineurin inhibitor, mycophenolate mofetil and prednisolone plus proton pump inhibitors as per routine practice. Patients diagnosed with BOS and on cyclosporine-based immunosuppressive regimen were switched to tacrolimus, had their immunosuppressive dose increased, and were administered a high-dose methylprednisolone pulse (10–15 mg/kg body weight).

†Only patients who had a follow-up of 3 months minimum were included in data analysis.

‡Non-responders were defined as patients who had a reduction if FEV₁ of more than 5% from baseline at start of ECP after 3, 6, or 12 months.

 

AE, adverse event; BOS, bronchiolitis obliterans syndrome; CF, cystic fibrosis; CMV, cytomegalovirus; ECP, extracorporeal photopheresis; FEV₁, forced expiratory volume in 1 second.

1. Jaksch P, et al. J Heart Lung Transpl. 2012;38(4S).