Ethnic Minority RA Consortium (EMRAC)

Ethnic Minority RA Consortium (EMRAC) Yusuf Yazıcı, MD Assistant Professor of Medicine, New York University School of Medicine Director, Seligman Center for Advanced Therapeutics & Behçet Syndrome Evaluation, Treatment and Research Center NYU Hospital for Joint Diseases, New York

Abbott BMS Celgene Centocor Genentech Janssen Merck Pfizer Takeda Disclosures

Background Current RCT population Differences among racial/ethnic groups A real world registry Pros and cons

Images courtesy of John Cush, MD. The Clinical Spectrum of RA

RA Takes Lives Death Disability Discomfort Iatrogenic Economic Years of Disease

RA in Ethnic groups? decline American/Alaskan Indians to Africans/Asians HLA-DR4*0401 varied frequency UK 0.8% Less in Afro-Caribbean Africa East and South, rare in West 0.9% US AA = Whites (0.5 1.0%) HLA-DRB1 in 30% AA *0404 Unrelated to dz activity BUT, as severe as Whites South America AA HLA-DRB1 infrequent Mild disease Asia Less severe in Asians HLA-DR4*0405

Ethnic Differences in Therapies Adverse effects MTHFR 677 C --> T SNP was associated with alopecia in African Americans (p = 0.032) 1 Normal BMD in JRA 2 Access/Adherence/Preference No differences 3 Disparity in biologic access (VA) 4 Decreased adherence 5 Less preference for aggressive Rx in AA, concern for toxicity 6 1. Ranganathan, P. et al, J. Rheum, 2008 2. Head, A. et al. J. Rheum, 2006 3. Ang, D, et al, J. Rheum, 2006 4. Berrios-Rivera, JP, et al. ACR, 2006 abstract #772 5. Garcia-Gonzalez, Clin Rheumatol, 2008 6. Constantinescu, F., et al. Med Care, 2009, Arthritis Care Res, 2009

Research and Interventional Strategies for Eliminating Ethnic Disparities in Rheumatic Diseases Research Documentation of disparities, identification of cause Mechanisms of disparity genetic, environmental, social, behavioral Identification of disparities in evaluation and treatment Intervention Self efficacy competence and ability of patients to monitor and manage their condition Racial lack of ethnic leadership and health professionals, stereotyping Literacy functional

U. S. Veterans with Rheumatoid Arthritis (VARA) Multi-center, IRB approved, RA registry since 2002 1 Eleven sites 1827 RA patients, 1822 patient-yrs, Male (90%), Elderly (mean 66.5 yrs) Disease duration, mean = 17.6 years Significant comorbidity Hypertension 55% Tobacco use 79% Hyperlipidemia 44% Diabetes mellitus 20% Coronary artery disease 18% BMI 30 kg/m 2 ~ 30% 2 Vitamin D insufficiency > 80%, primarily non-caucasian 3 1. Mikuls, T. et al. J. Rheumatol, 2007, 34(7), 1480-1484 2. Kerr, et al. Rheumatology I, Chap 12, 2012 3. Kerr, et al. J. Rheumatol, 2011

Association of Race/Ethnicity with RA Features (African American men vs. Caucasians men) No racial/ethnic differences in RF or accp status, radiographic disease, ESR, CRP, MHAQ, swollen joints, or DAS28 AA with higher number tender joints 5.7 vs. 3.3 (p = 0.03) AA with lower frequency of nodules 24% vs. 44% (OR = 0.32; 95% CI 0.13-0.81) Adjusted for age, site of enrollment, disease duration, smoking status J. Rheum, 2007;34:1480-84

CLEAR database Consortium for the Longitudinal Evaluation of African- Americans with early RA (2003) Osteopenia in 55%, osteoporosis in 16% (33% vs 5% if Caucasian normative data used) Vitamin D insufficiency common, not related to activity or severity Similar Xray progression to Caucasians (~ 60% in 3 yrs) IL4R SNPs, rs1801275 and rs1805010 with RA nodules in sero+ GWAS study of CCP+ Bridges, Lou. University of Alabama

Baseline characteristics of study cohort by current treatment of rheumatoid arthritis CORRONA: Association of MTX, anti-tnf with infection risk. Greenberg et al, Annals Rheum Dis, 2010

Ethnic Minority RA Consortium (EMRAC) 1. Detroit (Mosley-Williams, VAMC) 2. New York (Yazici, NYU) 3. Washington, DC (Nair, WHC/GTU)) 4. Washington, DC (Kerr, HUH) 5. St. Louis (Ince, PP) 6. Greenville (Treadwell, ECU) 7. New Orleans, (Espinoza, LSU) 8. Fort Lauderdale (Sherrer, PP) VAMC = Veterans Affairs Medical Center NYU= New York University PP = private practice WHC = Washington Hospital Center/Georgetown University ECU East Carolina University LSU = Louisiana State University 5 1 2 45 3 6 7 8

Methods Enrolment of IRB consented, physician-diagnosed RA patients meeting ACR diagnostic criteria (1987), of self-reported Collected data include patient demographics, comorbidities, RA disease related characteristics (MDHAQ, ESR, CRP, tender and swollen joint counts) and treatments To include all RA patients controls

EMRAC Demographics African-American Caucasian Hispanic Other Total p value N Age (years) Duration (years) 154 184 111 54 503 58.5 (14.0) 54.1 (18.9) 54.2 (15.0) 49.1 (16.0) 54.9 (16.6) 8.9 (8.9) 10.0 (10.9) 8.9 (9.3) 8.2 (8.7) 9.2 (9.7) 0.002* 0.864 Education (years) 13.8 (3.3) 15.7 (2.9) 12.4 (3.9) 15.7 (3.6) 14.4 (3.6) <0.001* Female [N (%)] 137 (89%) 154 (84%) 89 (80%) 47 (87%) 427 (85%) 0.231 African-Americans were older and less educated than Asians African-Americans were also less educated than Caucasians as were Hispanics Asians were more educated that Hispanics

Composite Disease Activity Indices by Ethnic Groups 14 12 Outcome Score 10 8 6 4 2 0 African-American Caucasian Hispanic Other (N=154) (N=184) (N=111) (N=54) RAPID3 [0-30] DAS28 [0-10] CDAI [0-76]

EMRAC: RHEUMATIC MEDICATIONS Prednisone [N (%)] DMARD [N (%)] Biologic [N (%)] African- American Caucasian Hispanic Other Total p 66 (43%) 60 (33%) 40 (36%) 18 (33%) 184 (37%) 127 (82%) 118 (64%) 77 (69%) 40 (74%) 362 (72%) 30 (19%) 75 (41%) 46 (41%) 19 (35%) 170 (34%) 0.249 0.002* <0.001* African-Americans had a smaller percentage of patients than Caucasians for the neither DMARD or Biologic category African Americans had a greater percentage of patients in the DMARD only category than Caucasians African Americans had a smaller percentage of patients in the biologics only category than Caucasians as well as smaller in the both DMARD and biologics category than Caucasians Similar findings when African Americans compared to Hispanics

DMARD and Biologic Use by Ethnic Group 100 80 82 Percent Using 60 40 43 33 64 41 36 69 41 33 74 35 20 19 0 African-American Caucasian Hispanic Other (N=154) (N=184) (N=111) (N=54) Prednisone DMARD Biologic

EMRAC: COMORBIDITIES N(%) Hypertension Asthma African American Caucasian Hispanic Other Total 63 (41%) 35 (19%) 20 (18%) 12 (22%) 130 (26%) 9 (6%) 14 (8%) 13 (12%) 5 (9%) 41 (8%) Diabetes 24 (16%) 6 (3%) 11 (10%) 4 (7%) 45 (9%) Cigarette Use (Ever) 40 (26%) 47 (26%) 19 (17%) 4 (7%) 110 (22%) p value <0.001* 0.372 0.001* 0.012 African-Americans had a larger percentage of patients than Caucasians, Asians, and Hispanics with hypertension African-Americans had a larger percentage of patients than Caucasians with diabetes mellitus

Comorbid Conditions by Ethnic Groups 45 Percent Positive 40 35 30 25 20 15 10 5 0 41 6 16 26 19 8 3 26 18 12 10 African-American Caucasian Hispanic Other (N=154) (N=184) (N=111) (N=54) 17 22 9 7 7 Hypertension Asthma Diabetes Smoking (Ever)

Disease Activity and Treatment by of EMRAC Disease Activity and Treatment by Race of EMRAC patients patients African- N 154 183 111 54 502 American Caucasian Hispanic Other Total P value RAPID3 [0-30] (N=461) 12.1 (7.2) 10.0 (6.8) 13.5 (7.2) 10.4 (7.8) 11.5 (7.3) 0.001* DAS28 [0-10] (N=127) 3.6 (1.4) 3.7 (1.5) 3.0 (1.9) 4.1 (1.8) 3.6 (1.5) 0.330 CDAI [0-76] (N=169) 12.2 (11.5) 14.5 (10.9) 10.5 (9.9) 15.5 (14.4) 13.0 (11.5) 0.347 DMARD [N (%)] 127 (82.5%) 117 (63.9%) 77 (69.4%) 40 (74.1%) 361 (71.9%) 0.002* Biologic [N (%)] 30 (19.5%) 74 (40.4%) 46 (41.4%) 19 (35.2%) 169 (33.7%) <0.001** Combination Therapy <0.001 Neither DMARD or Biologic 22 (14%) 42 (23%) 22 (20%) 9 (17%) 95 (19%) DMARD only 102 (66%) 67 (36%) 43 (39%) 26 (48%) 238 (47%) Biologic only 5 (3%) 24 (13%) 12 (11%) 5 (9%) 46 (9%) Both DMARD and Biologic 25 (16%) 51 (28%) 34 (31%) 14 (26%) 124 (25%) *Bonferroni corrected (P<0.008) comparisons: AA vs Caucasian (P<0.001) and AA vs Hispanic (P=0.012) **Bonferroni corrected (P<0.008) comparisons: AA vs Caucasian (P<0.001) and AA vs Hispanic (P<0.001) Bonferroni corrected (P<0.008) comparisons: AA vs Caucasian (P<0.001) and AA vs Hispanic (P<0.001)

Current EMRAC analyses Cardiac risk scores Hypothesis: Minorities will have higher scores than non -- minorities Dz activity at start and switch of biologics Hypothesis: Minorities will have higher DAS, etc at these time points compared to non - minorities Patient TJC/SJC parallels MD TJC/SJC Hypothesis: Minority RA patients are as reliable as non- minorities in TJC/SJC measurements Reasons for lack of use of biologics in minorities who are not at target Hypothesis: Minorities who have high disease activity are not treated with biologics (or change in DMARD therapies) because of comorbid conditions and lack of access Combo vs Mono use of biologics Hypothesis: There is a difference in RA patient profiles/variables between these treatment subsets Ethnic differences in AE s Are there Ethnic differences CCP+ vs CCP patients?

Still more to be done Education ACR Ethnic Minority Study Group NMA NQMF HUH Rheumatology Spring Symposium Access Specialty Care Treatment (Pharma patient assistance programs) Research African American Rheumatoid Arthritis Network (AARAN) Ethnic Minority RA consortium (EMRAC)?? RA in Caribbean

Conclusions Unmet need Real world data Different approaches to treatment? Different monitoring?