The application of Health Technology Assessment in the field of biologics: an evaluation of etanercept for treating Rheumatoid Arthritis
The application of Health TechnologyAssessment in the field of biologics: an evaluation of etanercept for treating Rheumatoid Ar thritisChiara 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 AnalisiValutazioni Economiche, Milan, Italy; **: Pfizer Italy; °°: Public Health and Infectious Diseases Department, Sapienza University of Rome, Italy
Rheumatoid ar thritis (RA) andbiologics 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
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 frameworkChapter 1: Epidemiology and burden of disease of RAChapter 2: Overview of biologic drugs for RAChapter 3: Biotechnology, efficacy and safety of etanerceptChapter 4: The costs of RA in the international and national contextChapter 5: Economic analysis of the use of etanercept in second line treatmentChapter 6: Organisational implications related to the use of etanercept in the Italian health care contextChapter 7: Ethical considerations
Epidemiology and burden of diseaseof 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, 2006Impact on mortality: reduction of 3-7 years in life expectancy indeveloped world.Impact on disability: 50-60% of patients no more able to work by 10years. Salaffi F, 2004; Sokka T, 2008
Epidemiology and burden of diseaseof 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
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
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
Economic analysis of etanerceptThe 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, 2002A 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.
Economic analysis of etanerceptThe 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 implicationsRA: 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
Ethical considerationsValues 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.itResearch Centre of Health Technology AssessmentInstitute of HygieneCatholic University of the Sacred HeartL.go F. Vito 1, 00168 Rome, ItalyPhone: +39 06 35001525