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Therapeutic
Window inRA. Myths,
Realities andOpportunities
Therapeutic
Window inRA. Myths,
Realities andOpportunities
Carlo Vinicio Caballero Uribe MDCarlo Vinicio Caballero Uribe MDUnidad de Reumatologa. Universidad delUnidad de Reumatologa. Universidad delNorte. Barranquilla. ColombiaNorte. Barranquilla. ColombiaCoordinador Comit de Investigaciones.Coordinador Comit de Investigaciones.Clnicas de Artritis Tempranas. ACR Clnicas de Artritis Tempranas. ACR
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"Muchos aos despus, frente al pelotn defusilamiento, el coronel Aureliano Buendahaba de recordar aquella tarde remota en quesu padre lo llev a conocer el hielo.
Macondo era entonces una aldea de 20 casasde barro y caabrava construidas a la orilla deun ro de aguas difanas que se precipitaban
por un lecho de piedras pulidas, blancas yenormes como huevos prehistricos.
El mundo era tan reciente, que muchas cosascarecan de nombre, y para mencionarlas habaque sealarlas con el dedo".
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Critical Window for Treating RA
van der Heijde D. Arthritis Rheum 1992;35:26Grassi W. Eur J Radiol 1998;27(Suppl):S18Schuna A. J Am Pharm Assoc 1998;38:728
Window of Opportunitty
DiseaseOnset
P r e m a
t u r e
D e a
t h a n
d
d i s c a p a c i
t yEarly Established End Stage
Radiographic progression occurs early andcontinues over the lifetime of a patient70% of patients have radiographic damagewithin the first 3 years
r
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Emerging Themes in Our Understanding of RA
Early diagnosis Early treatment
+Disease control of
signs and symptomsDamage preventionMaintain structural integrity
Preserve functionAND
Quality of Life
? = Remission
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Early RA. A Window of Opportunity? Editorials
Treating rheumatoid arthritis early: a window of opportunity? J O Dell 2002
The benefit of early Treatment in RA. R. Landew Understanding the window of opportunity concept in
early rheumatoid arthritis. M Boers 2003 Window of opportunity in early rheumatoid arthritis:
possibility of altering the disease process with earlyintervention. Quinn 2003 Window of opportunity . D Furst 2004
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The concept of a window of opportunityfor effective treatment of recent-onset RA
has been supported by 1 meta-analysis , 6RCTs and several comparative or observational studies (6)
* Combe et al Ann Rheum Dis 2006
10 studies , 5: 2000 and less5 2001-
Traditional DMARDs
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Patients Who Present Early to RheumatologistsAre More Likely to Show Improvement
Proportion Improving20%
0-1 1-2 2-5 5-10 >10
0.8
0.7
0.6
0.5
0.4
0.3
TJCSJCESR
Disease Duration(years)
Anderson JJ, et al.Arthritis Rheum.
2000;43:22-29 .
53% 43% 44% 38% 35%
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Early Rheumatoid ArthritisDefinitions
Inflammatory state of at least
2 years (Leiden)1 year (France)
6 months (Finland)12 weeks (Austria)*Criterios del Colegio Americano de Reumatologa
Breedveld F Clin Exp Rheum
2003;21(S):S100
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The natural history of inflammatoryarthritis
ONSET CHRONIC
persistence &
differentiation severitysusceptibility
g e n e t ic
h or m o n a l/r e pr o d uc t ive
g e n e t ic
h or m o n a l/r e pr o d uc t ive
g e n e t ic
h o rm o n a l/r ep ro d uc t ive
e n viro n me n ta l e nv ir o nm e n ta l
trea tment
en v ir on m e n t a l
trea tment
D Symmons, Joint and Bone.org 2004
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Aletaha, D et al. Ann Rheum Dis 2004;63:1269-1275
Attitudes to early rheumatoid arthritis:changing patterns.
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Attitudes to early rheumatoid arthritis:changing patterns (2)
Caballero CV , Londoo J, Chalem P. Rev Colomb Reumatol 2003Ann Rheum Dis. (Abstracts Book 2003)
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Therapeutic Window of Opportunity. Realities
Establish RA as a publichealth priority
Encourage acces to promptdiagnosis and treatment
Develope algorithms according our realities
Establish routine
epidemiologicalsurveillance
Educate people , patientsand doctors
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Certain issues affect the implementation of early andeffective treatment, including the lack of definitediagnosis criteria in early RA, delay in qualified medicalattention, and difficulty in identifying patients likely todevelop persistent disease or with risk factors for severe or erosive disease
First LA Position Paper. Rheumatology 2006
Qualified manpower availability to treat RA is
insufficientDeficient drug availability and access to therapyInadequate medical records and information
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Los Genericos y Biolgicos Impulsanel Crecimiento del Mercado
(MAT June 2003 Vs. Mat June 2002)
%0
%5
%10
%15
%20
%25
%30
Biotech Total Mkt Generics
Source: IMS HEALTH; Retail and Provider Perspective, 2003
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Gasto Pblico en salud como % del PIB y GastoGasto Pblico en salud como % del PIB y Gasto per capita en Salud per capita en Salud (En US Dlares)(En US Dlares)
$1
$ .1 3
$ .1 6
$ .1 3
C a n a d a
U S A
O E C D - E u r
L a t i n A m e r it h e C a r ib b e
Source: IDB, Latin America after a decade of reforms, Londoo and Szkely
,3 0
,6 6 ,6 3,7 0
C a n a d a
U S A
O E C D - E u
L a t in A m e r t h e C a r ib b
GP % PIB Gasto per capita
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Composicin de los Gastos Nacionales de Salud por Subsector en Latino America
, %158
, %85
, %172, %390
, %195
Gobierno Central GOB LOCAL
Seguridad Social Gasto de Bolsillo
Gastos Indirectos
Source: IDB, Latin America after a decade of reforms, Londoo and Szkely
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Enfermedades de Alto Costo enColombia. Min Proteccin Social 2002
Enf de AltoCosto
No de pacientes Costo ( Millones US)
Trasplante renal 196 31782UCI 6272 208900
Dilisis 5446 675121
AR 1600 250434
Ciruga Cardiaca 5553 193917
SIDA 3665 185478
Quimio y Radio 13579 321552
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Community Education Needs To BeImproved
Inexistance of Gov.Programs (93%)
Inexistance of publiceducation programs (86%)
Lack of media information(82%)
Lack of information among people (81%)
Massive media difussion isnecessary (75%)
Second Consensus PANLAR/GLADAR on Education and treatment of RA. Chile 2005
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Delays Occur
Patients delay
Hospitals delay
Physiciansdelay
Outpatient ClinicUSA 95: 36 weeksNetherlands 98: > 3 months
Spain 06: 14 monthsNorway 06: 16 weeks
Total Lag
TimeMod of D Symmons, Joint and Bone.org 2004O Palm ARD 2006Eular 2006
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Age, of establishment, (range in years) 51 (21 85)
Female % 94
Low socio-economic level, % 51
RA with less than 1 year of evolution, % 29.8
RA with 2 years of evolution, % 54.3
RA with 3 years, % 79.8Time of follow-up, average (months) 11
Delay to diagnosis (X) (months) 15
Baseline Demographic Characteristics in 94Patients with recent-onset RA in B/quilla.
Caballero CV, Vivero S. Panlar Abstracts 2006
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Diagnostic Lag Time in 100 patientsof a HMO. Barranquilla 2006
0
5
10
15
20
25
30
35
40
45
2 3 4 5 6
Patient'sPhycisian'sHospital's
Time (Months)
% Of Patients
Caballero 2006. data on file
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50-74% of visits
13%
32%
11%
14%
16%
14%
never
1-24% of visits
25-49% of visits
75-99% of visits
always
"Across all routine visits of patients with RA under yourcare (not including clinical trials), what % of these visitsincludes a formal tender and swollen joint count?"
Tender and swollen joint count inroutine visits
Pincus. Ann Rheum Dis 2006
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Therapeutic Window in Early RA.Opportunities
Overcome rheumatologicfrontiers through peopleseducation
Encourage implementation of EACs
More real life studies
Test established hypothesis Promote utilization of
objective outcome measures Evaluate overall outcomes
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Patients presenting with arthritis of more than one joint should be referred to and seen by a rheumatologist,ideally within 6 weeks after the onset of symptoms
Although the level of evidence supporting the content of this recommendation is rather low (category III or IV),there was general agreement that a recommendation
regarding the recognition of arthritis and regarding earlyreferral should be included.
* Combe et al Ann Rheum Dis 2006
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3 swollen joints
Involvement of MCF or MTF
Morning Stiffness 30 min.
Early derivation:
Early Referral Recommendation for Newly
Diagnosed RA: Evidence Based Development of aClinical Guide.
Emery P. et al. Ann Rheum Dis, 61:290, 2002 ..
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What should we offer ?
Rapid access Full diagnostic/prognostic
assessment
Early therapeutic intervention Access to allied health
professionals, e.g. physiotherapy,occupational therapy and podiatry
services Patient education Early re-assessment
Outpatient Clinic
Quinn, Emery. Best Practice and Res Clin Rheumatol 2004
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Whether a 'window of opportunity' exists during whicheffective therapy might lead to
cure is still an open issue andshould be the focus of clinicaltrials in the near future.
Rheumatological communityhas to establish RA as a healthpriority to improve acces tocare and to a window of opportunity
Conclusions
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