This document provides a health technology assessment of etanercept for treating rheumatoid arthritis. It includes 7 chapters that evaluate the epidemiology and burden of RA, biologic drugs for RA including etanercept, the economic impacts, organizational implications, and ethical considerations of using etanercept. The assessment finds that etanercept improves quality of life when combined with methotrexate compared to methotrexate alone, and has a cost-effectiveness ratio of €25,130 per quality-adjusted life year gained, making it a reasonable treatment option.

1. The application of Health Technology
Assessment in the field of biologics: an
evaluation of etanercept for treating
Rheumatoid Ar thritis
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

2. Rheumatoid ar thritis (RA) and
biologics
RA is a chronic inflammatory multifactorial disease
targeting joints which leads to the destruction of
cartilage and bone.
 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

3. 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.

4. 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

5. 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
Alamanos Y, 2006
Impact on mortality: reduction of 3-7 years in life expectancy in
developed world.
Impact on disability: 50-60% of patients no more able to work by 10
years. Salaffi F, 2004; Sokka T, 2008

6. Epidemiology and burden of disease
of RA
Cimmino, 1998 Marotto, 2005 Salaffi, 2005 Della Rossa, 2010
Region Liguria Sardegna Marche Toscana
Study period 1991-1992 2002-2003 2004 2006-2007
N 3.294 30.264 2.155 26.709
Setting General practitioners General General practitioners General practitioners
practitioners
Methods Questionnaire + ACR 1997 Questionnaire + Questionnaire + ACR 1997 Questionnaire + ACR 1997
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% F: 0,73% n.a. F: 0,63%
M: 0,13% M: 0,19% 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

7. Biologics in the treatment of RA
Efficacy
All 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
Safety
Risk of withdrawals due to adverse events
Singh JA, 2009 Singh JA, 2011

8. Etanercept
Weinblatt 2010
Weinblatt 1999
 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, Moots RJ 2011
 215,0 per 100.000 in patients managed with adalimumab.
 Data confirmed by the British Society for Rheumatology Biologic Register

9. 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.
Ciocci A, 2001; Leardini G, 2002
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.

10. 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

11. Organisational implications
RA: early diagnosis fundamental
 general 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

12. 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

13. 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.

14. Thank for your kind attention!
For further information:
Italian Journal of Public Health World: www.ijph.it
Research Centre of Health Technology Assessment
Institute of Hygiene
Catholic University of the Sacred Heart
L.go F. Vito 1, 00168 Rome, Italy
Phone: +39 06 35001525