Health Disparities in SLE Those we can address as health professionals Those we can address as citizens Those that are immutable

The Lupus Initiative Curriculum: Note to Reviewers Suggested changes from previous reviewers have been compiled but are not reflected in the slides that follow. Any revisions you recommend will be added to those already received and, following this round of review, A small panel of lupus educators will evaluate all comments received and decide what will be incorporated into the final slide modules. Thank you for your participation in this process. Sharing your expertise helps ensure the best educational materials are available to future medical and health professionals.

Distribution of US Population Race and Ethnicity 2008 and 2050

Problems with Available Data Sets Many studies have small numbers of patients and may not be representative Many studies have data from 30–40 years ago Many studies of racial/ethnic differences relate to the general population, not specifically to those with SLE Access to healthcare and disease outcome may vary geographically, so some data sets may not be broadly applicable

Why There Is a Problem Mortality Odds ratio compared with females P value Odds ratio compared with females Male (ns) Odds ratio compared with whites Black (ns) Hispanic (ns) Odds ratio Below the poverty line 2.109 0.006 Disease activity at baseline 1.144 <.001 Poverty and lack of education are public health concerns Adapted from LUMINA

Who Gets SLE? Women > men: 2–3:1 before puberty; 9:1 after menarche; 2:1 after menopause African ancestry, Hispanics, Asians: whites ~3–4:1

Ascertainment Matters We were wrong for a long time and thought blond women got lupus. First study showing blacks have more lupus

Why Women? Genetics A 2nd X chromosome (increased incidence in XXY) Demethylation of TLR7, CD40 ligand (epigenetics) Hormones Estrogen is permissive (altered estrogen metabolism in blacks to more estrogenic compounds) Androgen is protective

Why Certain Races/Ethnicities? Genetics Different risk alleles in different populations: PTPN22 in whites FcRIII158F (low binding) in Asians FcRIIB in all (the allele confers a loss of function as the protein is not in lipid rafts. Interestingly, it protects against malaria)

Are There Nongenetic Risk Factors? The incidence of many autoimmune diseases is increasing. This appears to be true for lupus also. There have been many speculations why; none is proven: Hygiene hypothesis Estrogen exposure Vitamin D deficiency Obesity

Prevalence Rate (%) Vitamin D Deficiency by Race and Gender We are all Vitamin D deficient, but blacks, Hispanics and Asians more so

Patients with 25-D Levels <10 ng/mL 25-D Levels are Low in Black and Hispanic Lupus Patients and Inversely Correlates with Disease Activity Patients with 25-D Levels <10 ng/mL 25-D Levels (ng/mL) Blacks Asians Whites Hispanics Blacks Asians Whites Hispanics 25-D Blood Levels (ng/mL) SLEDAI

Major Manifestations Blacks have More renal disease with more pure membranous disease Cardiovascular events at an earlier age; more carotid plaque, more hypertension but lower cholesterol and triglycerides More discoid disease Hispanics have Cardiovascular events at an earlier age Asians have More hemolytic anemia and more thrombocytopenia Northern Europeans have More skin manifestations than Southern Europeans

Serology Chinese More anti-DNA than blacks or whites More anti-Ro Less anticardiolipin Blacks More anti-Sm than Chinese or whites More anti-U1RNP

Presentation in Different Groups Age Antibodies Organs Blacks Younger Sm, RNP Discoid, kidney Asians Kidney Hispanics malar rash, kidney Whites Older Skin, CNS Men ? Pediatric Kidney, CNS These data are based on relatively small studies. It does appear that disease is more active in blacks and Hispanics at time of diagnosis. Whether this has to do with properties of the disease or issues relating to the healthcare system and physicians is not clear. It is important to recognize that untreated lupus progresses. Treat before there is irreversible tissue damage.

Progression of Disease Differences in affected organs: more renal disease and more membranous nephropathy in blacks Rate of accumulation of damage is higher in blacks and Hispanics Damage accrual relates to poverty. There may be a genetic component also: lack of DRB1*0301 in Hispanics, presence of DQB1*0201 in whites. Mortality rate is higher in blacks, Hispanics, Asians

Renal Disease Is a Major Cause of Morbidity and Mortality There is more renal disease in pediatric-onset SLE and in blacks 60% of patients with adult-onset SLE develop renal disease 80% of patients with pediatric-onset SLE develop renal disease 50% of ESRD in SLE is in blacks, although they account for <25% of affected individuals

Multivariate Predictors of Progression of Proliferative Lupus Nephritis Proverty, health insurance, and hypertension are not immutable

Hypertension Predictors of hypertension in patients from the LUMINA cohort by multivariable logistic regression analyses (n = 382) Hypertension and renal disease are a bad combination. We must treat hypertension

Total Age-Adjusted Coronary Heart Disease Mortality Among US Females Age 35 and Older, 1998 SLE increases the risk of coronary heart disease in all groups

Factors Related to Outcome Patient issues Inactivity Self-efficacy (related to poverty and education) Adherence to therapeutic regimen Obesity Physician issues Willingness to engage patients in therapy decisions Willingness to discuss exercise and diet (both black and white MDs less likely to discuss these topics with black patients) Cultural competency Issues for both patient and physician Communication (language barriers) Health education

Factors Related to Outcome Societal issues Access to healthcare Poverty Education

Survival in Patients with Severe Lupus Nephritis on the Basis of Race P <.029, black vs white; NS for black vs other and for other vs white).

Renal Transplants Transplant access Blacks < Hispanics < whites receive transplants Organ donation less in blacks (both living and cadaver) Medicaid is a risk for no transplant

Transplant Survival Black recipients (n = 1304) Non-black recipients (n = 1149)

Renal Transplants Transplant outcome Both adult and pediatric blacks do less well (almost double mortality in black children) More recurrent disease in blacks Reasons for poor outcome Poverty Hypertension less well controlled in blacks Blacks have a longer time on dialysis It is not yet clear if there is a genetic component to transplant outcome in SLE: IL-6, rantes, CCR5, TNF, CTLA-4,TLR4 (both donor & recipient)

Cardiovascular Outcome Contributing problems Hypertension Diabetes Adequate medical management Whites > blacks and Hispanics Management Access to cardiac catheterization Men > women Whites > minority Physicians less likely to discuss exercise, diet with blacks

Estimated Age-Adjusted Prevalence of Overweight and Obesity among US Females Ages 20–74 Years, 1988–1994 Source: NHANES III [1988–94] (not specific for SLE patients)

Treatment Are there important racial/ethnic differences in how to use medications or in response? Mycophenolate Higher dose needed in blacks (3 vs 2 gm) Cyclophosphamide ? less good renal response in blacks Rituximab ? greater response in blacks Antihypertensive medication Beta blockers less effective in blacks

Treatment Genetic contribution to efficacy and toxicity TPMT Toxicity and efficacy of azathioprine levels lower in women, minorities P450 Efficacy of cyclophosphamide: no evidence of racial differences

Medication Adherence No difference in taking medications Blacks Hispanics Whites Follow-up visit 57% 53% 62% Prescription 87% 95% 84% Reason for lack of follow-up: Whites: feel better Blacks, Hispanics: difficulty making appointment

Clinical Research Minority patients are underrepresented in clinical studies

Clinical Trials Concept of “the good study patient” emphasizes someone who is compliant and has a strong social network No difference among racial/ethnic groups in willingness to participate in clinical trials if previously enrolled Physicians need to put more effort into enrolling minorities in clinical research and clinical trials. Patient education is a useful recruitment strategy

Conclusions—You Can Make a Difference as a Physician and a Citizen Remediable issues: patient and physician Hypertension Diabetes Self-efficacy Access to organ donation Access to cardiac catheterization Engagement in clinical research and clinical trials Obesity Cultural competency Societal issues Stress Poverty/access to healthcare/insurance

Physician Misconceptions Conscious misconceptions: There are no disparities 63% of physicians think the healthcare system has no racial or ethnic bias (compared with 43% of the entire population and 25% of blacks) Minorities are unlikely to engage in clinical studies Unconscious misconceptions: Minorities engage in unhealthy behaviors Smoking, immunizations, fruit and vegetable intake are not different between blacks and whites Minorities are unable/unwilling to participate in their own care

Recommendations (The IOM Model) Inform healthcare professionals on the nature and extent of disparities Use treatment guidelines to avoid unconscious bias Implement patient education programs Include measures of racial and ethnic disparities in performance measures