1. 1 LUPUS & DISABILITY Arthur Weinstein, MD, FACR, MACP Professor of Medicine, Georgetown University Medical School Director of Rheumatology, Washington Hospital Center SSA Panel on Compassionate Allowances for Autoimmune Disease 03/16/2011

2. 2 Connective Tissue Disorders SLE Dermatomyositis Polymyositis Undifferentiated CTD Sjogren’s syndrome Scleroderma

3. 3 LUPUS: What is it? It is a SYSTEMIC disease NOT localized It is a MULTI-ORGAN (multi-system) disease not single organ – eg skin, joints, kidneys It is an AUTOIMMUNE INFLAMMATORY disease, but not an infection – the normally “protective” immune system is hyperactive and inward looking and “hurtful” [Single organ autoimmune diseases – thyroid, diabetes, multiple sclerosis, myasthenia gravis] Lupus=Systemic Lupus Erythematosus=SLE

4. 4 How Rare is Lupus? It is not! 0.15 % - 150-250/100,000 >500,000 in the USA >10,000 in MD 9X commoner women than men 3x commoner AA vs Cauc’s also commoner in Asians and Hispanics

5. 5 LUPUS & Women, Minorities and Children: An unfair and discriminatory disease increased in women increased in AA women peak incidence in women of childbearing years - a serious disease of young people more severe in AA, Hispanics more severe, more renal disease in children higher cardiovascular mortality in women, AA women

6. 6 6 Central Nervous System Seizures, Psychosis, Strokes, Headaches Cognitive dysfunction, Neuropathies, Myelopathy, Depression, Fatigue Eyes and Mucous Membranes Ulcers in the Eyes, Nose, Mouth or Vagina, Sjogren’s Syndrome Heart and Lungs Pericarditis, Myocarditis Endocarditis, Pleuritis, Heart attacks Kidneys Edema, Hypertension, Proteinuria Cell Casts, Renal Failure, Dialysis Musculoskeletal Arthralgia, Myalgia, Arthritis,Jaccoud’s Arthropathy, Myositis Blood Anemia, Thromobocytopenia Leukopenia, Thromobosis, TTP, Circulating Autoantibodies and Immune Complexes Skin Butterfly Rash, Cutaneous Lesions, Photosensitivity, Alopecia, Vasculitis Raynaud’s Phenomenon How Can Lupus Affect the Body?

7. 7 Is Lupus Difficult to Diagnose? Yes and No Often starts as a “flu”- fever, aches and pains, fatigue but persists Mild rash harder to spot in dark skin or may not be present Often abnormalities in the routine blood tests - anemia, low WBC (like viral infection) Key Question: Could I have Lupus? Blood tests (autoantibodies- ANA, anti-DNA and others are good diagnostic markers) What about lupus flares? Lupus is chronic with recurrent mild or severe flares Current biomarkers helpful but imperfect Is it active lupus, is it comorbidity such as infection, is it both?

8. 8 8 SLE Genes Immune Dysregulation Environment DO WE KNOW WHAT CAUSES LUPUS?

9. 9 Can Lupus Be Fatal? YES! 1950 – 50% mortality in 3yrs 2010 – 10% mortality in >5yrs BUT these are young women and men and sometimes children more severe illness and higher mortality in AA, Hispanics, children

10. 10 Do the Drugs Work for Lupus? Treatments can be life saving Treatments do not cure lupus In general, high risk treatments do better in the short term (treating severe flares) than over long periods In general, the most potent treatments have the highest risk of side effects

11. 11 Medications Approved by FDA for Treatment of SLE 2010 St Joseph Aspirin Ecotrin Hydroxychloroquine Corticosteroids –Prednisolone –Dexamethasone –Solu-Medrol Nothing Approved for Lupus in >50 years!! (President Dwight D Eisenhower)

12. 12 What Drugs are Used to Treat Lupus ? prednisone – low ( 1mg/kg/day) hydroxychloroquine (Plaquenil) – rash, fatigue, joint, muscle pains immunosuppressives –methotrexate, azathioprine (Imuran), mycophenolate (CellCept) –cyclophosphamide (Cytoxan) I.V. – remission induction - renal, brain inflammation

13. 13 Is there anything new? Yes! NEW Biologic Agents – “designer drugs” belimumab (Benlysta) Human Genome Sciences, Rockville, MD **Nov 16,2010 - Arthritis Panel of the FDA voted 13 to 2 to approve Benlysta for Lupus** epratuzumab rituximab (Rituxan) And others – directed against elements (B cells/proteins) in the hyperactive immune system of Lupus

14. 14 SLE and Connective Tissue Disorders Clinical Features related to disability Constitutional and multisystem effects Chronic, no cure Exacerbations (flares) and remissions unpredictable but usually treatable Treated with immunosuppressive medications – side effects Comorbidities due to organ damage, to medication side effects, to long term disease/treatment effects and to other factors (eg psychological)

15. 15 Work Disability in SLE Extent of the Problem Cohort of 159 patients with SLE working since diagnosis (Partridge et al: Arthritis Rheum 1997; 40:2199) –40% quit work completely average of 3.4 years after diagnosis –substantial job modifications –predictors of early work disability – lower education status (no college), physical rather than mental job, greater disease activity at time of diagnosis

16. 16 FeatureOdds ratio 95% confidence interval p Value* Age1.0681.018–1.1190.007 Sex (male)4.4891.277–15.7830.019 Poverty2.8601.167–7.0040.021 Total disease duration1.2111.061–1.3800.004 SLAM-R average1.2481.129–1.379<0.001 SDI at the last visit1.3621.115–1.6630.002 Systemic lupus erythematosus in a multiethnic US cohort LUMINA Factors predictive of work disability by multivariable logistic regression analysis Only p = 0.05 are recorded. SLAM-R, Systemic Lupus Activity Measure — Revised SDI, Systemic Lupus International Collaborating Clinics Damage Index;. Inception cohort of 273 SLE patients (C, AA, H) (Bertoli et al: Ann Rheum Dis 2007; 66:12) 19% self-report of disability at 5 years (25% in AA)

17. 17 Time to the occurrence of self-reported work disability in the LUMINA cohort: (A) entire cohort and (B) by ethnic group. Bertoli A M et al. Ann Rheum Dis 2007;66:12-17 © Most disability within 2-3 years

18. 18 How Can Lupus Cause Disability? Severe organ disease Renal (50-60% adult; 70-80% children) CNS Lungs Heart acute and chronic kidney failure (app 5%), hemodialysis, kidney transplantation encephalitis, spinal cord inflammation, strokes lung hemorrhage, pulmonary hypertension valvular disease, myocardial infarction

19. 19 End Stage Renal Disease – women, AAs, children US Renal Data System Ped SLE 171 (5%) Adult SLE 1342 (1.4%) Ped Other 3276 Adult Other 93, 694 Mean age at HD15.23911.658.5 % Female79834447 % Black66553538 Sule et, Pediatr Nephrol 2010 Higher mortality in Pediatric and Adult SLE ESRD than others

20. 20 Lupus and Disability Effects of Medications Cortisone toxicity – diabetes, hypertension, obesity, cataracts, osteoporosis, avascular necrosis (need hip and knee replacements), infections leading to acute and chronic disability (shingles) Other immunosuppressive medications - serious infections, sometimes fatal Sterility (cyclophosphamide)

21. 21 Cognitive Changes in SLE Acute: lupus cerebritis medication – steroid psychosis CNS infection Chronic: stroke multi-infarct dementia chronic cognitive impairment of uncertain cause

22. 22 The Cruelty of Coronary Artery Disease in Lupus higher risk than diabetes 498 women with SLE - 33 developed CAD (6.6%) (f/u 13 years, ages 15-74) 2208 women in Framingham study - 36 developed CAD (1.6% 35-44 age group up to 50X increased incidence compared to normal in Framingham youngest 34 - in SLE group any age – even in the 20’s 36% deaths in lupus due to cardiovascular (CV) disease - heart attacks and strokes Black women with SLE were 20 years younger than black women matched controls at time of CV death

23. 23 Disability in Lupus Summary Depends on Disease-specific Factors: disease severity specific organ involvement and damage medications used and complications long term morbidity, including cardiovascular disease Depends on demographic factors: race and gender socioeconmoic status education level and type of work (eg physical vs sedentary)