the application of health technology assessment in the field of biologics: an evaluation of...
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The application of Health Technology Assessment in the field of biologics: an evaluation of etanercept for treating Rheumatoid ArthritisTRANSCRIPT
Chiara de Waure*, Maria Lucia Specchia*, Flavia Kheiraoui*, Giorgio L. Colombo°^, Roberto
Di Virgilio**, Angela Maria Giardino**, Chiara Cadeddu*, Francesco Di Nardo*, Giuseppe La Torre°°,
Maria Luisa Di Pietro*, Walter Ricciardi*
*: Research Center of Health Technology Assessment, Institute of Hygiene, Catholic University of the Sacred Heart, Rome, Italy;°: Università degli Studi di
Pavia, Facoltà di Farmacia, Italy; ^: S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; **: Pfizer Italy; °°: Public Health and Infectious Diseases
Department, Sapienza University of Rome, Italy
The application of Health Technology Assessment in the field
of biologics: an evaluation of etanercept for treating Rheumatoid
Arthritis
RA is a chronic inflammatory multifactorial disease targeting joints which leads to the destruction of cartilage and bone.
Rheumatoid arthritis (RA) and biologics
First line treatment: disease-modifying antirheumatic drugs (DMARDs) Methotrexate (MTX) most commonly used.
Second line treatment: combination therapy with DMARDs and biologics. Biologics prevent the inflammatory pathways; they are:• TNF-alpha blockers: etanercept, infliximab, adalimumab,
certolizumab, golimumab• Interleukin inhibitors: tocilizumab, anakinra• Monoclonal anti-CD20 antibody: rituximab• T-cell co-stimulation modulator: abatacept
Objective and methods
Analyse the value of etanercept in the treatment of RA with respect to its use as first choice in the second line treatment.
Multidisciplinary and multidimensional evaluation through:
Literature reviews (burden of disease, clinical manifestations, management and costs of RA),
Mathematical model economic analysis,
Organizational and ethical analysis.
The HTA framework
Chapter 1: Epidemiology and burden of disease of RA
Chapter 2: Overview of biologic drugs for RA
Chapter 3: Biotechnology, efficacy and safety of etanercept
Chapter 4: The costs of RA in the international and national context
Chapter 5: Economic analysis of the use of etanercept in second line treatment
Chapter 6: Organisational implications related to the use of etanercept in the Italian health care context
Chapter 7: Ethical considerations
Impact on mortality: reduction of 3-7 years in life expectancy in developed world.
Epidemiology and burden of disease of RA 10,7 cases per
1.000
5 cases per 1.000
3,3 cases per 1.000
3,5 cases per 1.000
Impact on disability: 50-60% of patients no more able to work by 10 years.
Alamanos Y, 2006
Salaffi F, 2004; Sokka T, 2008
Epidemiology and burden of disease of RA
Cimmino, 1998 Marotto, 2005
Salaffi, 2005 Della Rossa, 2010
Region Liguria Sardegna Marche ToscanaStudy period 1991-1992 2002-2003 2004 2006-2007
N 3.294 30.264 2.155 26.709Setting General
practitionersGeneral
practitionersGeneral
practitionersGeneral
practitioners
Methods Questionnaire + ACR 1997
Questionnaire + ACR 1997
Questionnaire + ACR 1997
Questionnaire + ACR 1997
Prevalence (95%CI)
0,33% (0,13-0,53%)
0,46% 0,46% (0,33-0,59%)
0,40% (0,32-0,47%)
Prevalence by gender
F: 0,51%M: 0,13%
F: 0,73%M: 0,19%
n.a. F: 0,63%M: 0,14%
Length of the disease
< 2
years
2-5
years
5-10
years
>10
years
Total
Percentage of workers changing their work
because of RA
17,9% 20,5% 20,4% 30,1% 22,7
%
ANMAR, SIR, CENSIS, 2004
Biologics in the treatment of RA
EfficacyAll biologic drugs have been demonstrated effective in combination to MTX in comparison to MTX alone.In particular, adalimumab, alone or in combination to MTX, has been proven superior to placebo ± MTX in the short and long term. Also infliximab did demonstrate the same results.
Wiens A, 2010
SafetyRisk of withdrawals due to adverse events
Singh JA, 2009 Singh JA, 2011
Etanercept
French Research Axed on Tolerance of Biotherapies (RATIO): risk of TBC 116,7 (95%CI: 10,6–222,9) per 100.000 patient years. 9,3 per 100.000 patient years in patients
treated with etanercept, 187,5 per 100.000 in patients given
infliximab, 215,0 per 100.000 in patients managed
with adalimumab.
Weinblatt 1999
Weinblatt 2010
Moots RJ 2011
Data confirmed by the British Society for Rheumatology Biologic Register
Economic analysis of etanercept
The cost of illness analysis demonstrated that around 40% are Direct Medical Costs with the remaining representing Indirect Costs increasing with the severity of the disease.
A cost-utility analysis has been performed from the National Health Service perspective in order to:- compare etanercept, infliximab and adalimumab to DMARDs - in patients with severe RA enrolled in 2003-2004 in the register of the Italian Study Group on Early Arthritis (GISEA). Patients with an Health Assessment Questionnaire - HAQ - score ≥ 1,5 have been considered.
Ciocci A, 2001; Leardini G, 2002
Economic analysis of etanercept
The identification and quantification of resources have been performed with respect to GISEA data, while the imputation of costs has been performed by means of ex factory prices and health service tariffs.
The outcome has been analysed in terms of HAQ variation.
Costs Utility
ICER
DMARDs € 5.595
0,288
Adalimumab
€ 11.136
0,449 € 34.273
Etanercept
€ 10.957
0,501 € 25.130
Infliximab
€ 10.892
0,496 € 25.407
Organisational implications
RA: early diagnosis fundamentalgeneral practitioners education in order to:
- early detect potential patients,- strive the consultation of specialists,- allow the timely beginning of treatment.
Multidisciplinary management Chronic Care Model
http://www.improvingchroniccare.org
Ethical considerations
Values considered: life, health and quality of life promotion, individual choices respect, pursue of community benefit.
Risk/Benefit ratio no differences from placebo in terms of safety in RCTs and good profile demonstrated by meta-analyses.
Quality of life it improves with the use of etanercept plus MTX in comparison to MTX only.
The defense of individual choices: communication!The justice: improve equal access to care and drugs!
http://www.improvingchroniccare.org
Conclusions
RA: chronic illness often cast aside by Public Health perspective, but with high considerable social impact because of involvement of age and gender groups which are contributory and active.
HTA as a support for decision-makers in the informed evaluation of impact deriving from the employment of biologics: optimisation of second line treatment.
Thank for your kind attention!
For further information:
Italian Journal of Public Health World: www.ijph.it
Research Centre of Health Technology AssessmentInstitute of HygieneCatholic University of the Sacred HeartL.go F. Vito 1, 00168 Rome, ItalyPhone: +39 06 35001525