Therapeutic

Window in
RA. Myths,
Realities and
Opportunities
Carlo Vinicio Caballero Uribe MD
Unidad de Reumatología. Universidad del
Norte. Barranquilla. Colombia
Coordinador Comité de Investigaciones.
Clínicas de Artritis Tempranas. ACR
"Muchos años después, frente al pelotón de
fusilamiento, el coronel Aureliano Buendía
había de recordar aquella tarde remota en
que su padre lo llevó a conocer el hielo.

Macondo era entonces una aldea de 20

casas de barro y cañabrava construidas a la
orilla de un río de aguas diáfanas que se
precipitaban por un lecho de piedras
pulidas, blancas y enormes como huevos
prehistóricos.

El mundo era tan reciente, que muchas

cosas carecían de nombre, y para
mencionarlas había que señalarlas con el
dedo".
 Critical Window for Treating RA
Radiographic progression occurs early and
continues over the lifetime of a patient
r

Premature Death and discapacity

70% of patients have radiographic damage
within the first 3 years
Disease Onset

Early Established End Stage

Window of Opportunitty

van der Heijde D. Arthritis Rheum 1992;35:26

Grassi W. Eur J Radiol 1998;27(Suppl):S18
Schuna A. J Am Pharm Assoc 1998;38:728
 Emerging Themes in Our
Understanding of RA
Early diagnosis Early treatment

+
Disease control of Damage prevention
signs and symptoms Maintain structural integrity

Preserve function
AND
Quality of Life

? = Remission
 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. Landewé
● 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 early intervention. Quinn 2003
● Window of opportunity . D Furst 2004
The concept of a “window of opportunity”
for effective treatment of recent-onset RA
has been supported by 1 meta-analysis , 6
RCTs and several comparative or
observational studies (6)

10 studies , 5: 2000 and less

5 2001-
Traditional DMARDs
•* Combe et al Ann Rheum Dis 2006
Patients Who Present Early to Rheumatologists
Are More Likely to Show Improvement
Proportion Improving 20%
0.8
TJC
0.7 SJC
ESR
0.6

0.5

0.4

53% 43% 44% 38% 35%

0.3
0-1 1-2 2-5 5-10 > 10
Disease Duration (years)
Anderson JJ, et al. Arthritis Rheum. 2000;43:22-29.
 Early Rheumatoid Arthritis
Definitions

Inflammatory state of at least

●2 years (Leiden)
●1 year (France)
●6 months (Finland)
●12 weeks (Austria)
*Criterios del Colegio Americano de Reumatología

Breedveld F Clin Exp Rheum

2003;21(S):S100
 The natural history of inflammatory
arthritis
persistence &
susceptibility differentiation severity

genetic genetic genetic

hormonal/ hormonal/ hormonal/
reproductive reproductive reproductive

treatment treatment

environmental environmental environmental

ONSET CHRONIC
•D Symmons, Joint and Bone.org 2004
Attitudes to early rheumatoid arthritis:
changing patterns.

Aletaha, D et al. Ann Rheum Dis 2004;63:1269-1275

Copyright ©2004 BMJ Publishing Group Ltd.
Attitudes to early rheumatoid arthritis:
changing patterns (2)

Caballero CV , Londoño J, Chalem P. Rev Colomb Reumatol 2003

Ann Rheum Dis. (Abstracts Book 2003)
Therapeutic Window of
Opportunity. Realities

● Establish RA as a public
health priority
● Encourage acces to prompt
diagnosis and treatment
● Develope algorithms
according our realities
● Establish routine
epidemiological
surveillance
● Educate people , patients
and doctors
“Certain issues affect the implementation of early and
effective treatment, including the lack of definite
diagnosis criteria in early RA, delay in qualified medical
attention, and difficulty in identifying patients likely to
develop persistent disease or with risk factors for severe or
erosive disease”

•Qualified manpower availability to treat RA is

insufficient
•Deficient drug availability and access to therapy
•Inadequate medical records and information

•First LA Position Paper. Rheumatology 2006

Los Genericos y Biológicos Impulsan
el Crecimiento del Mercado
(MAT June 2003 Vs. Mat June 2002)

30%

25%

20%

15%

10%

5%

0%
Biotech Total Mkt Generics

Source: IMS HEALTH; Retail and Provider Perspective™, 2003

Gasto Público en salud como % del PIB y Gasto
per capita en Salud (En US Dólares)

7,0%
6,6% Canada $1.628 Canada
6,3%

$1.310 $1.314
USA USA

3,0% OECD - Europe

OECD - Europe

Latin America and

$102 the Caribbean
Latin America and
the Caribbean

•GP % PIB •Gasto per capita

Source: IDB, “Latin America after a decade of reforms,” Londoño and Székely
Composición de los Gastos Nacionales de Salud por
Subsector en Latino America

19,5% 15,8%
8,5%

17,2%
39,0%

Gobierno Central GOB LOCAL

Seguridad Social Gasto de Bolsillo
Gastos Indirectos

Source: IDB, “Latin America after a decade of reforms,” Londoño and Székely
Enfermedades de Alto Costo en
Colombia. Min Protección Social 2002

Enf de Alto
No de pacientes Costo (Millones US)
Costo
Trasplante renal 196 31782
UCI 6272 208900
Diálisis 5446 675121
AR 1600 250434
Cirugía Cardiaca 5553 193917
SIDA 3665 185478
Quimio y Radio 13579 321552
Community Education Needs To Be
Improved

● Inexistance of Gov.
Programs (93%)
● Inexistance of public
education programs (86%)
● Lack of media information
(82%)
● Lack of information among
people (81%)
● Massive media difussion is
necessary (75%)
Second Consensus PANLAR/GLADAR on Education and treatment of RA. Chile 2005
 Delays Occur…

Patient’s delay

Physician’s
delay

Hospital’s delay

USA 95: 36 weeks Outpatient Clinic

Total Lag Netherlands 98: > 3 months
Spain 06: 14 months •Mod of D Symmons, Joint and Bone.org 2004
Time
•O Palm ARD 2006
Norway 06: 16 weeks •Eular 2006
Baseline Demographic Characteristics in 94
Patients with recent-onset RA in B/quilla.

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, % 79.8
Time of follow-up, average (months) 11
Delay to diagnosis (X) (months) 15

Caballero CV, Vivero S. Panlar Abstracts 2006

 Diagnostic Lag Time in 100 patients
of a HMO. Barranquilla 2006
•45

•40

•35

•30
% Of Patients

•25 •Patient's
•Phycisian's
•20 •Hospital's

•15

•10

•5

•0
•2 •3 •4 •5 •6

Time (Months)

Caballero 2006. data on file

 Tender and swollen joint count in
routine visits
"Across all routine visits of patients with RA under your
care (not including clinical trials), what % of these visits
includes a formal tender and swollen joint count?"
never
13%
1-24% of visits
32%
25-49% of visits
11%
50-74% of visits
14%
75-99% of visits
16%
always
14%

•Pincus. Ann Rheum Dis 2006

Therapeutic Window in Early RA.
Opportunities

● Overcome “rheumatologic
frontiers” through people’s
education
● Encourage implementation of
EACs
● More “real life” studies
● Test established hypothesis
● Promote utilization of
objective outcome measures
● Evaluate “overall” outcomes
… “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 early
referral should be included.

•* Combe et al Ann Rheum Dis 2006

 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
Outpatient Clinic
services
● Patient education
● Early re-assessment
•Quinn, Emery. Best Practice and Res Clin Rheumatol 2004
Conclusions

• Whether a 'window of
opportunity' exists during which
effective therapy might lead to
cure is still an open issue and
should be the focus of clinical
trials in the near future.

• Rheumatological community
has to establish RA as a health
priority to improve acces to
care and to a ‘’window of
opportunity”