Perspective on Rheumatoid Arthritis 2006 and Beyond A Latin American Scope
Eduardo Acevedo MD, DR, FACR President 1990-1992, Peruvian Rheumatology Society Professor: Universidad Nacional Mayor de San Marcos
Head: Rheumatoogy Department, Hospital G. Almenara
Clinica San Felipe, Lima Perú
A Latin American Perspective on Musculoskeletal Disorders
Musculoskeletal or rheumatic diseases are the major cause of morbidity throughout the world, having a substantial influence on health and quality of life, and inflicting an enormous burden of cost on health systems
Dr.G. Harlem Brundtland.* The Burden of Musculoskeletal Conditions at the Start of the New Millennium. World Health Organization. Geneva, 2003
*Director-General of the World Health Organization
A Latin American Scope
Latin America and the Caribbean: 551 million inhabitants (World Bank, 2005) 70% of this population is older than 15 years of age The four most important ethnic origins: Mestizos, Latin AfroAmericans, Amerindians, Caucasians (GLADAR, 2006)
National gross income per capita: $2209 (World Bank, 2005)
Life expectancy at birth: 70 years (CELADE, 2000)
A Latin-America Scope in:
Rheumatoid Arthritis
Rheumatoid Arthritis Prevalence
Spindler A et al. J Rheumatol 2002;29:1166–70 0.2% Argentina Senna ER et al. J Rheumatol 2004;31:594–7 0.5% Brazil
Cardiel MH et al. Clin Exp Rheumatol 2002;20:617–24 0.3% México Medina M et al. J Clin Rheum 2006;12(suppl) 0.3% Perú
Genes in Rheumatoid Arthritis (RA): Pathogenic Role of T-cell Activation and co-stimulation in RA
Stastny (peruvian rheumatologist) showed the relationship between rheumatoid arthritis (RA) and the human leucocytespecific antigenic genes of the major histocompatibility complex (MHC). This is a notable finding because the human leukocyte antigen (HLA) is the molecular key responsible for antigen presentation from the antigen presenting cell (APC) to the T cell, thereby originating the first signal for activation and co-stimulation for initiation of the specific or adaptive immune response
P Stastny – Mixed lymphocyte cultures in rheumatoid arthritis. J Clin Invest 1976;57:1142–1157 – Association of the B-cell alloantigen Drw4 with rheumatoid arthritis. N Engl J Med 1978;298:869–71
Influence of Alleles HLA-DR in Rheumatoid Arthritis
Influence of HLA-DRB shared epitope on susceptibility to and clinical expression of RA in Chilean patients. Ann Rheum Dis 1997;56:191
Gonzalez A, Nicovani S, Massardo L, Aguirre V, Cervilla V, Lanchbury JS, Jacobelli S
DRB1
Susceptibility *0404 or *0408 SE (SD) SE (DD)1 Severity Moderate
RA
N=129 (%)
Controls
N=97 (%)
OR
p value
24 (19) 70 (54) 26 (20)
5 (6) 29 (30) 4 (4)
3.00 3.00 6.95
0.01 0.0004 0.0009
SE (DD) – Vasculitis or extra-articular manifestations
RA=rheumatoid arthritis; OR=overall response rate; 1DD vs absence from SE=7.5-fold increase in risk for AR; SE=shared epitope; SD=single dose to SE; DD=double dose
Influence of Alleles HLA-DR in Rheumatoid Arthritis
Influence of HLA-DR alleles on RA: susceptibility and severity in Argentine patients. J Rheumatol 2001;28:1486
Citera G, Padulo LA, Fernandez G, Lazaro MA, Rosemffet MG, Maldonado Cocco JA
DRB1
RA
N=140 (%)
Controls
N=202 (%)
OR
p value
Susceptibility
DR41 70 (50) 47 (23) 3.25 0.00005
Severity (Rx)
Alleles from SE don’t show differences in severity Subtype *1001 – > Radiologic damage (13% vs 3%; p=0.03)
RA=rheumatoid arthritis; OR=overall response rate; SE=shared epitope; 1*0404 (38%) – *0401 (29%)
Influence of Alleles HLA-DR in Rheumatoid Arthritis
Tumor necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with RA Ann Rheum Dis 2001;60:7921
Castro F, Acevedo E, Ciusani E, Angulo JA, Wollheim FA, Sandberg-Wollheim M
Susceptibility
TNF-α6
More frequent in P vs C (RR 2.35; p<0.015)
HLA-DRB1
*1402 – allele more common in RA (33.3% vs 15.4%, RR 2.74; p<0.023) Significantly more frequent in RA
Haplotype HLA-DRB1*1402 - DQB1*0301 - DQA1*0401
Polymorphisms TNF and *1402 contribute independently to susceptibility to RA in Peruvians Mestizos; RA=rheumatoid arthritis; RR=risk ratio
Influence of Alleles HLA-DR in Rheumatoid Arthritis
RA association in Colombian population is restricted to HLA-DRB1*04 QRRAA alleles. Genes Immun 2002;3:56
Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M
Frequency of alleles HLA-DRB1 in Colombian women (NO)
DRB1 Group *01 Group *03 Group *041 Group *14 Group *1001
RA
N=83 (%)
Controls
N=90 (%)
OR 4.1 -
P value NS NS <0.001 NS NS
16 (19) 13 (15) 39 (47) 8 (10) (0)
12 (13) 12 (13) 16 (18) 22 (24) 3 (3)
RA=rheumatoid arthritis; OR=overall response rate; 1Group *0403 (7.2%) – 0404 (9.6%); NS=not significant
WORK DISABILITY IN RA
Author Makisara (1982) Yelin (1987) Reisine (1989) Hernandez (1990) Wolfe (2002) Odegard (2005) Medina(Almenara Hospital 2006) Country UK USA USA Mexico USA Sweden Peru % of Disabled People 50%(405/202) 50% (306/158) 43%(284/122) 28.4%(162/46 ) 32.7%(5012/1639) 40%(526/210) 34.3% (300/103) Years after Dx 10 10 5 12 10 7 13
Economic Impact of Rheumatoid Arthritis – Costs
Series
ArizaAriza (México) 1997
Studied population
3
Studied population
Tertiary center
Direct medical cost US $
228–2661
Associated factors
Not evaluated
Kaleh (EUA) 2003
Audisio (Argentina) 2003 Pineda (Colombia) 2005 Medina *(Peru:Hospital Almenara2006)
7527
52
Multicentric database
National hospital National hospital Social security system
9519 per year
677.5 half years
HAQ, comorbidities
Not associated to: age, disease duration, HAQ Not evaluated
191
4891 per year
645
635.96 per year
HAQ
HAQ=Health Assessment Questionnaire . * J Clin Rheumatol 2006:12 Suppl
Patient Profile for Rheumatoid Arthritis in PERU
Description Mestizo population 97.5%
Urban population
Duration of disease, years Age at diagnosis, years Diagnosis delay, years % of extra-articular manifestations Functional capacity I: II: III: IV: Work disability
91.3%
13.22 ± 10.24 43 ± 13.6 2 ± 0.4 61.7% 16.8% 47.5% 26.3% 9.4% 34.3%
Source: 661 rheumatoid arthritis patients. Hospital-AlmenaraI. Lima, Perú 2004.; J Clin Rheumatol 2006:12 Suppl
Rheumatoid Arthritis in Almenara Network Cohort, Lima, Perú: Female to Male Ratio by Age Group, 2004
8 7.91 7.52 7 6 5.33 5 4 3 2.67 2 1 0 <20 20–24 25–29 30–34 35–39 40–44 45–49 4.82 5.33 6.19
7.84
6.27
6.17
Female to male ratio
4.06 3.1
2.57
2.17
50–54
55–59
60–64
65–69
70– 74
75–79
>79
Age group
Source: 2606 rheumatoid arthritis patients; Total population: 860243. Almenara Network. Lima, Perú 2004. J Clin Rheumatol 2006:12 Suppl
Economic Impact of Rheumatoid Arthritis – Costs
4000
3000
Cost per patient/US $
* 55
18 46
2000
1000
0
-1000
N=21 <2 years of RA ($421.7)
N=21 2–10 years of RA ($518.13)
N=21 >10 years of RA ($968.0)
Disease duration (years)
Source: 645 rheumatoid arthritis patients. Hospital-Almenara. Lima, Perú 2004. J Clin Rheumatol 2006:12 Suppl. RA=rheumatoid arthritis
Grupo Latinoamericano de Artritis Reumatoide: GLADAR
Non-profit, non-governmental organization Latin American initiative of rheumatology physicians dedicated to:
— — —
—
Execution of multicenter studies in patients with RA in the region Organization of concensus for therapy Stimulating service projects focused on health and care for patients with RA Improving understanding of this disease in the Latin American community
GLADAR Motivation based on :
— —
Shortage of epidemiologic information Necessity of quality/quantification of the Latin American reality of RA
LA own characteristics
Demographic Socio-economic Environment
GLADAR Cohort (Analysis March 31, 2006)
Countries
Argentina
Brazil Chile Colombia Costa Rica Cuba Dominican Republic Ecuador El Salvador México Panama Perú Uruguay Venezuela Total: 14
Centers
5
12 2 5 1 1 1 2 1 8 1 3 1 3 46
Patients
140
261 61 115 23 35 23 51 30 172 8 65 22 87 1093
GLADAR Cohort: Demographic data
Major ethnics groups (N=1059) Mestizos n 473 % 43
Caucasians
ALA Amerindians
343
204 39
31
19 4
GLADAR 2006
GLADAR Cohort: Distribution by Gender and Ethnic Groups
Ethnic groups Total Gender F M Caucasians F M ALA F M Mestizos F M Amerindians F M 930 163 287 56 173 31 407 66 36 3 Patients 85% 15% 84% 16% 85% 15% 86% 14% 92% 8% 12:1 6:1 6:1 5:1 F:M Ratio 6:1 P value
0.476
GLADAR 2006
Arnulfo Nava Mexico
Leading role as coordinators
María Eugenia Suárez Almazor (USA)
1. 2. 3. 4. 5. 6. 7. 1. 2. 3. 4. 5. 6. 7.
SUBJECTS Education
Patient education (1)
María E Suárez-Almazor Julio Hofman (Argentina) Manoel Bertolo (Brazil) Mario Moreno (Ecuador) Angel Achurra (Panamá) Evelyn Hess (USA) Napoleón Peña (Venezuela) Carlo Vinicio Caballero (Colombia) Horacio Venarotti (Argentina) Pedro Miranda (Chile) Osvaldo Caliste (Cuba) Nilmo Chávez (Guatemala) Juan Angulo (Perú) Kate Lorig (Estados Unidos) 1. 2. 3. 4. 5. 6. 7.
Therapy
Drug safety surveillance (5)
Roger Levy (Brazil) Francisco Caeiro (Argentina) William Otero (Colombia) Rubén Montufar (El Salvador) Margarita Duarte (Paraguay) Jaime Hernández (Uruguay) Héctor Gatica (Chile)
Mario Cardiel (México)
Community education (2)
Indications of biologics for incomplete responders to classic DMARDs (6)
1. 2. 3. 4. 5. 6. 7. Alberto Millán (Venezuela) Pablo Riedemann (Chile) Rafael Valle (Colombia) Francisco Girón (Honduras) Armando Calvo (Perú) Boulos Haroui (Canada) Sergio Jacobelli (Chile)
Bernardo Pons-Estel (Argentina)
Health policy and decisions (3)
1. 2. 3. 4. 5. 6. 7. Enrique Soriano (Argentina) Sebastian Radominski (Brazil) Loreto Massardo (Chile) Oscar Uribe (Colombia) Marlene Guibert (Cuba) José A. Herrera (Venezuela) Adriana Silvestre (Argentina)
Programs for early detection and appropriate treatment of RA (7)
1. Eduardo Acevedo (Perú) 2. Luis José Catoggio (Argentina) 3. Fernando Cavalcanti (Brazil) 4. Miguel Gutiérrez (Chile) 5. Renato Guzmán (Colombia) 6. Leonor Barile (México) 7. Alicia Ramagli (Uruguay)
Carlos Pineda (México)
Other health professionals education
1. Ieda Laurindo (Brazil) (4) 2. Maria Luisa Gil (Bolivia) 3. Carlos Fuentealba (Chile) 4. Ricardo Sáenz (Costa Rica) 5. Francisco Rosas (México) 6. Rafael Alba Féris (Rep. Dominicana) 7. Sergio Aragón (Nicaragua)
The role of classic DMARDs (8)
1. 2. 3. 4. 5. 6. 7. Rolando Espinosa (México) John Londoño (Colombia) Licia da Mota (Brazil) Nilzio Antonio da Silva (Brazil) Claudio Galarza (Ecuador) Arnulfo Nava (México) Alfredo Sánchez (Perú)