Treatment of Rheumatoid Arthritis in Latin America - EULAR 2014

Juan-Manuel Anaya, MD, PhD
Center for Autoimmune Diseases Research (CREA)
Universidad del Rosario
Méderi Hospital Universitario Mayor
Bogota, Colombia
www.urosario.edu.co/crea
Trends in the Treatment of
Rheumatoid Arthritis in Latin America

Trends in the Treatment of
 What Latin America & the
Caribbean (LAC) are like and
what we can learn about
rheumatoid arthritis from LAC.
 Treatment of rheumatoid
arthritis in LAC.

 The Americas were first inhabited by people
crossing the Bering Land Bridge from
northeastern Asia into Alaska well over 10,000
years ago.
 Europeans arrived after 1492 following
Christopher Columbus´ voyages.
 African people were captured and taken to
America by the transatlantic slave trade from
the 16th to the 19th centuries.
 Latin America & the Caribbean have millions of
tri-racial people of European, African and
Amerindian ancestry.

 Latin America & the Caribbean is a region
of the Americas where Romance
languages (i.e., those derived from
Latin) – particularly Spanish, Portuguese,
and French – are primarily spoken.
 Area: 21,069,501 km² (7,880,000 sq mi),
almost 3.9% of the Earth's surface
or 14.1% of its land surface area.
 Population: ~ 600 million and an
economic growth rate of ~4%.

• Autoimmune diseases, such as rheumatoid
arthritis, are complex traits in which both
genetic and environmental factors are
incriminated in their etiopathogenesis.
• The expression of these diseases varies
depending on ethnicity and geography.
• The large and diverse population of Latin
America & the Caribbean is a powerful
resource for elucidating the genetic basis
of these complex traits due to its high
admixture.

Admixture in Latin America
Sans M. Hum Biol 2000;72:155.
503711Cuba
80<10<10Peru
80<10<10Ecuador
>80<10>10Bolivia
<4010>50Venezuela
266.567.5Argentina
43~057Chile
201565Brasil
1-207-15>80Uruguay
56341Mexico
>15>15<60Colombia
Amerindian
(%)
African
(%)
European
(%)
Country

Amerindian Ancestry Influences Rheumatoid Arthritis
• The prevalence of RA is higher than expected among some Amerindian
groups (Tlingit, Yakima, Pima, and Chippewa Indians).
Del Puente A, et al. Am J Epidemiol. 1989;129:1170-8.
Ferucci ED, et al. Semin Arthritis Rheum. 2005;34:662-7.
• Compared to Caucasians, RA in Latin America has an earlier age at onset
and affects more women than men (5.2:1) with some clinical
characteristics that differ from RA presentation in men.
Barragán-Martínez C, et al. Gend Med 2012; 9:490-510.
• Loci associated with Amerindian ancestry in Latin American patients with
RA were found in the “Genómica de artritis reumatoide” (GENAR) project
López Herráez D, et al. Arthritis Rheum 2013;65:1457-67.

PolyautoimmunityFamilial Autoimmunity
Familial Autoimmunity and Polyautoimmunity
are frequent in Latin Americans
Clustering of autoimmune diseases is not random
Anaya JM. Autoimmun Rev 2014;13:423-6.
Cárdenas-Roldán J, et al. BMC Med 2013;11:73.
Anaya JM. Arthritis Res Ther 2010;12:147.
Anaya JM, et al. Expert Rev Clin Immunol 2007;3:623-35

Disease in first-degree relatives Parents Offspring Siblings
Systemic lupus erythematosus 25 (2,1%) 7 (0,6%) 39 (3,3%)
Rheumatoid arthritis 19 (1,6%) 0 13 (1,1%)
Autoimmune thyroid disease 12 (1%) 0 4 (0,3%)
Systemic sclerosis 0 0 1 (0,08%)
Polymyositis 1 (0,08%) 0 0
Familial Autoimmunity is frequent in Latin American patients with SLE
GLADEL cohort (N =1,177)
Alarcón-Segovia D, et al. Arthritis Rheum 2005;52:1138-47.
 High familial aggregation of RA in Latin American families with
SLE (ls: 3.3, lp: 5.3).
 A higher percentage of Mestizo SLE patients had relatives with
autoimmune disease (54.9%) compared with non-Mestizo
patients (41.1%) (p=0.001).

Factors Influencing Polyautoimmunity
in Systemic Lupus Erythematosus
Variable AOR 95% CI p
Gender (female) 2.30 1.03 5.15 0.043
Articular involvement 2.02 1.26 3.23 0.003
Familial autoimmunity 1.61 1.14 2.28 0.007
Anti-Ro Ab 1.54 1.10 2.16 0.013
Origin
(Colombia vs Spain)
1.78 1.40 2.27 < 0.0001
Rojas-Villarraga A, et al. Autoimmun Rev. 2010;9:229-32.

Ameridian Ancestry Influences Polyautoimmunity
in Colombians
Amerindian ancestry European ancestry
p: 0.001 p: 0.003
Molano-González N et al. Submitted

HLA-DRB1*04 Influences the Risk of Rheumatoid Arthritis
in Latin Americans
Delgado-Vega & Anaya. Autoimmun Rev 2007;6:402.

Delgado-Vega & Anaya. Autoimmun Rev 2007;6:402.
Shared Epitope is a risk factor for Rheumatoid Arthritis
in Latin Americans

Lee et al. J Rheumatol 2007;34:43
TNF -308 A is a Risk Factor for Rheumatoid Arthritis
in Latin Americans

Anaya et al. 2005 [298:308]
Combined [Fixed]
Ramirez et al. 2012 [394:434]
PTPN22 (1858 T) is a Risk Factor for Rheumatoid Arthritis
in Colombians
Anaya JM, Gomez LM, et al. Genes Immun. 2005;6:628-31.
Ramirez et al. Exp Rheumatol 2012;30:520-4.

Rheumatoid Arthritis
Colombians
Ramírez et al. Clin Exp Rheumatol 2012
Systemic Lupus Erithematosus
Colombians
Anaya et al. Genes Immun. 2005;6:628.
Ramírez et al. Clin Exp Rheumatol 2012
Argentinians
Orrú et al. Hum Mol Genet 2009;18:569.
PTPN22 (1858 T) is a Pleiotropic Autoimmune Allele
in Latin Americans
Sjögren´s Syndrome
Colombians
Anaya et al. Genes Immun. 2005;6:628.
Type 1 Diabetes
Colombians
Anaya et al. Genes Immun. 2005;6:628-31.
Brazilians
Chagastelles et al .Tissue Antigens 2010;76:144.
Rassi et al. Ann N Y Acad Sci. 2008;1150:282.

Brazilian Guidelines for the Diagnosis of Rheumatoid Arthritis
• Diagnosis of early RA (< 12 months) is of a summit importance because
early diagnosis exerts beneficial effects on radiological and functional
prognosis compared to later diagnosis.
• The 2010 ACR/EULAR criteria identify more patients with early RA than
does the 1987 ACR criteria. However, the rate of false-positive cases is
higher with the newer criteria.
• For established RA discriminatory powers of the 2010 ACR/EULAR and
the 1987 ACR criteria are similar.
• Smoking increases the disease activity of RA and reduces clinical and
functional responses over time. However, there is no sufficient
evidence regarding its influence on radiological disease progression.
Mota LM, et al. Rev Bras Reumatol 2013;53:141-57.

• Rheumatoid factor (RF) measurement is related to prognosis
(i.e., radiological progression and mortality).
• The sensitivity of anti-CCP is similar to that of RF, but its specificity
is higher, particularly in the early disease stages.
• Anti-CCP evaluation is recommended in patients with a clinical
suspicion of RA and negative for RF.
• RA progression is more severe in patients with extra-articular
manifestations.
• Conventional radiography must be used in diagnostic and
prognostic assessments. When needed and available, US and MRI
should also be used.

• The PTPN22 gene polymorphism is associated with RA.
Although it is not predictive of specific therapeutic responses
to biological therapy, it is predictive of remission when
associated with anti-CCP. Alone or in combination with HLA-
DRB1 (SE), the PTPN22 polymorphism allows estimations of
radiological progression.
• The HLA-DRB1 gene seems to play a more important role in the
prediction of poor prognosis relative to the progression,
activity, severity, and mortality of RA.

• GLADAR, a prospective, observational, multicenter,
multinational inception cohort of 1093 adult patients with
early RA (1 year from the first RA symptoms), from 46
centers in 14 Latin American countries, followed for 24
months.
• Female: 85%
• Rheumatoid factor (+): 76%
• Mean age at diagnosis: 46.5 (SD, 14.2) years,
• Mean disease duration at the first visit: 5.8 (SD, 3.8) months.
• Women had earlier onset than men (median 44.6 vs. 49.7
years, p<0.001)
Cardiel MH, et al. J Clin Rheumatol 2012;18:327-35.
Massardo L, et al. J Clin Rheumatol 2009;15:203-10.
Soriano ER, et al. Rheumatology (Oxford). 2008;47:1097-9.
Cardiel MH, et al. Rheumatology (Oxford) 2006;45 Suppl 2:ii7-ii22.
Pons-Estel BA et al. Ann Rheum Dis 2008;67(Suppl II):336

In Early RA, extra-articular manifestations are present in 10%,
and erosive disease is observed in 27.5% of patients. Joint
erosions are observed more frequently in RF-positive patients
and in those with no, or partial medical insurance coverage.
Pons-Estel BA et al. Ann Rheum Dis 2008;67(Suppl II):336
Low/low-middle socioeconomic status influences disease activity
in early RA.
Massardo L, et al. Arthritis Care Res (Hoboken). 2012;64:1135-43.
Patients have a low understanding of their disease.
Werner AM, et al. Rev Méd Chile 2006; 134: 1500-6
Cadena J & Anaya JM. Arthritis Rheum 2003;49:738-40.

Characteristic AOR 95% CI
Age at onset 1.04 1.02-1.06
Polyautoimmunity 3.22 1.20-8.75
Abdominal obesity 9.8 5.42-17.69
House duties 23.17 7.8-68.82

Sarmiento-Monroy JC, et al. Arthritis 2012;2012:371909.
Cardiovascular Disease in Latin American Patients
with Rheumatoid Arthritis

• DMARD as initial treatment: 75%
• MTX alone or in combination: 60.5%
• Antimalarials: 32.1%
• Sulfasalazine: 7.1%
• LEF: 4%.
• Combination therapy as initial treatment: 26%.
MTX + Antimalarials: 70%
• Biologics: 1%.
• Corticosteroids: 64%
Cardiel MH, et al. J Clin Rheumatol 2012;18:327-35.

Treatment of Rheumatoid Arthritis in Latin America
Burgos-Vargas R, et al. Reumatol Clin 2013;9:106-12.

• There are differences between the various recommendations,
especially regarding the criteria for beginning biological therapies,
hierarchic sequence for using available biological drugs, and for
suspending or switching them.
• Systematic review of the literature vs. opinion of experts and
consultants.
• The recommendations for treatment of RA should be updated more
frequently.
Fernandes et al. Rev Bras Reumatol 2011;51:220-30.

Rheumatology Biological Registries in Latin America
Titton DC, et al. Rev Bras Reumatol. 2011;51:152-60
De la Vega M, et al Rev Arg Reumatol. 2013;24:08-14
Registries have been established for
studying the long-term effects of
treatment for RA, especially with
respect to safety.
BIOBADASAR (Argentina)
BIOBADABRASIL (Brazil)
BIOBADAMEX (Mexico)
BIOBADAURUGUAY (Uruguay)

Biological Therapy in Rheumatoid Arthritis in Argentina
Chaparro del Moral R et al. Rev Arg Reumatol. 2013;24:18-26

b S.E. P-value AOR
Lack of efficacy 1.39 0.52 0.008 4.0
Drug omission (forgetfulness) 1.03 0.31 0.001 2.8
Hope for a quick response 0.71 0.28 0.01 2.0
Public vs. Private insurance 1.55 0.47 0.001 4.7
Factors Associated with Noncompliance with Biological Therapy
in Argentine Patients with Rheumatoid Arthritis
Chaparro del Moral R, et al. Rev Arg Reumatol 2013;24:18-26

Anti-TNF therapy Survival
Ventura-Ríos L, et al. Reumatol Clin 2012;8:189-94.

Reason BIOBADAMEX
N= 1,481
BIOBADASER
N= 5,493
BSRBR
N= 10,391
Adverse effect 19,1% 41% 21%
Inefficacy 33.6% 39% 22%
Remission 17,0% 3% NA
De la Vega M, et al. Rheumatol Int 2013;33:827-35.
Reasons for Suspending Biological Therapy

1. Early diagnosis and proper treatment of comorbidities are
recommended.
2. The specific treatment of RA should be adapted to the presence of
comorbidities.
3. Angiotensin-converting-enzyme inhibitors or angiotensin II receptor
blockers are preferred to treat systemic arterial hypertension.
4. In patients diagnosed with RA and diabetes mellitus, the
continuous use of a high cumulative dose of corticoids should be
avoided.
Management of Comorbidities
in Patients with Rheumatoid Arthritis
Pereira IA, et al. Rev Bras Reumatol 2012;52:474-95.

5. Statins should be used to maintain LDL cholesterol levels under 100
mg/dL and the atherosclerotic index lower than 3.5 in patients with
RA who have other comorbidities.
6. Metabolic syndrome should be treated.
7. Performing non-invasive tests to investigate subclinical
atherosclerosis is recommended.
8. Greater surveillance for the early diagnosis of occult malignancy is
recommended.
9. Preventive measures of venous thrombosis are suggested.

10. Bone densitometry is recommended in RA patients over the age of
50 years and in younger patients on corticoid therapy at a dose
greater than 7.5 mg for over three months.
11. Patients with RA and osteoporosis should be instructed to avoid
falls, to increase their dietary calcium intake and sun exposure, and
to exercise.
12. Calcium and vitamin D supplementation is suggested.
Bisphosphonates are suggested for patients with T score < –2.5 on
bone densitometry.
13. A multidisciplinary team, with the active participation of a
rheumatologist, is recommended to treat comorbidities.

Biosimilars
 A molecule that is “highly similar” to a
reference biotherapeutic product confirmed
by a comparability exercise and showing
similar quality, safety, and efficacy.
 They promote cost containment and favor
the sustainability of modern health systems
in a panorama of aging population,
demographic transition towards chronic
diseases like RA, costly health technologies,
and limited resources.
Desanvicente-Celis Z, et al. Immunotherapy. 2012;4:1841-57.
Desanvicente-Celis Z, et al. Biosimilars 2013;3:1-17.
 Biosimilars are available in Mexico, Brazil, Chile, Ecuador, Bolivia, Peru,
Argentina, Panama, Guatemala, Costa Rica, and Colombia.
Similar Biotherapeutic Products
Different Parties Affected by the Regulation and Marketing

Conclusions and Challenges
• RA in Latin America and the Caribean differs from other
regions in the world.
• Make RA a public health priority, knowing its socioeconomic
impact in terms of its high cost and burden on the health-care
system.
• Burgos-Vargas R, et al. Reumatol Clin 2013;9:106-12.
• Building own evidence-based practice through research.
• Education!
• « Traiter vite et fort! »
– Early Arthritis Clinics
• Marcos J, et al. General characteristics of an early arthritis cohort in
Argentina. Rheumatology 2011;50:110-6.
• Arbeláez-Cortés A, et al. The Cali early arthritis clinic.
Biomed Res Int 2014;2014: in press.
• Provide access to medications. Low cost - Price regulation.

Gracias! “How can we not hope that someday, when
neighborliness, cooperation and respect have
fulfilled their mission, the whole American continent
will be a vast alliance of dignity and civilization
brought about by languages and traditions?”
“¿Como no desear que algún día, cuando la vecindad
, la colaboración y el respeto hayan cumplido su
misión, todo el continente americano sea una vasta
alianza de dignidad y de civilización propiciada por las
lenguas y por las tradiciones?”

Treatment of Rheumatoid Arthritis in Latin America - EULAR 2014

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

En vedette

En vedette (20)

Similaire à Treatment of Rheumatoid Arthritis in Latin America - EULAR 2014

Similaire à Treatment of Rheumatoid Arthritis in Latin America - EULAR 2014 (20)

Dernier

Dernier (20)

Treatment of Rheumatoid Arthritis in Latin America - EULAR 2014