The application of Health Technology Assessment in the field of biologics: an evaluation of...

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