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Systemic Lupus Erythematosus: An Update

Systemic Lupus Erythematosus: An Update. Michelle Petri MD MPH Johns Hopkins University School of Medicine Baltimore, Maryland USA. Faculty Disclosures. Clinical Trials HGS/GSK Medimmune Pfizer TEVA Anthera UCB Consultant Genentech Lilly Merck Serono. Why Do I Have Lupus?.

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Systemic Lupus Erythematosus: An Update

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  1. Systemic Lupus Erythematosus:An Update Michelle Petri MD MPH Johns Hopkins University School of Medicine Baltimore, Maryland USA

  2. Faculty Disclosures • Clinical Trials • HGS/GSK • Medimmune • Pfizer • TEVA • Anthera • UCB • Consultant • Genentech • Lilly • Merck Serono

  3. Why Do I Have Lupus? 2/3 Genetics 1/3 Environmental

  4. Manhattan Plot of GWAS Criswell LA. The Rheumatologist. 2011;February:26-32.

  5. What are Gene Signatures?

  6. Genes That Define the LDG-Enriched NeutrophilGene Signature

  7. Environmental Triggers of SLE • Ultraviolet light • Drugs • Smoking‡ • Infections • Pet dogs* • Lab workers† • Silica†† • Mercury** • Pesticides ††Parks CG, et al. Arthritis Rheum. 2002;46:1840–1850. *Chiou S-H, et al. Lupus. 2004;13:442–449. †Zarmbinski MA, et al. J Rheumatol. 1992;19:1380–1384. **Cooper GS, et al. J Rheumatol 2004;31:1928. ‡Costenbader KH, et al. Arthritis Rheum 2004;50(3):849-857. Costenbader KH, Karlson EW. Autoimmunity 2005;38(7):541-547. Freemer, MM, et al. Annals Rheum Dis 2006;65:581-584. Majka DS, Holers VM. Annals Rheum Dis 2006;65:561-563.

  8. Why Do Men Get Lupus?

  9. Men vs Women

  10. An Ounce of Prevention is Worth a Pound of Cure

  11. Hydroxychloroquine(Plaquenil)is a Long-Term Medicine in Lupus For Prevention

  12. Hydroxychloroquine as Background Therapy

  13. Hydroxychloroquine May Prevent Thrombosis Wallace, et al. Arthritis Rheum. 1987;30:1435-6; Petri et al, Arthritis Rheum. 1994;37 (Suppl. 9):S297; Ruiz-Irastorza et al, Lupus. 2006;15:577-83; Tektonidou et al, Arthritis Rheum. 2009;61:29-36; Jung et al, Arthritis Rheum. 2010;62:863-8

  14. Low Vitamin D is Part of Lupus

  15. Vitamin D Deficiency in Human SLE

  16. 25-OH Vitamin D May (or May Not) Be Inversely Associated with Blood Pressure • Inverse association of 25-OH vitamin D and systolic blood pressureScragg R, et al. Am J Hypertens 2007;20:713-9. • PTH may mediate most of the association between 25-OH vitamin D and BP, which is not significant when adjusted for BMIHe JL, Scragg RK. Am J Hypertens 2011;24:911-7. • Vitamin D was not associated with BP in Puerto RicoCaro et al. P R Health Sci J 2012;31:123-9.

  17. Vitamin Reduced Thrombosis in Some Clinical Studies • Cancer RCT: calcitriol+docetaxel vs. docetaxel p=0.01 Beer et al. Br J Haematol 2006;135:392-4. • General population • lowest tertile of vitamin D: 37% (15-64%) rate of VTE Brøndum-Jacobsen et al. J Thromb Haemost 2013;11:423-31. • Higher rates of VTE in African-Americans Grant et al. Am J Hematol 2010;85:908. • TE are seasonal: highest risk in winter; sunbathing reduces rise of VTE by 30% Lindqvist et al. J Thromb Haemost 2009;7:605-10. • Cardiovascular Honolulu Heart Program: Low vitamin D predicted 34 yr incident stroke in Japanese-American men HR 1.22 (1.02-1.47), p=0.038 Kojima et al. Stroke 2012;43:2163-7. • Asian Indian cohort: mean vitamin D lower in CAD p = 0.036 Shanker et al. Coron Artery Dis 2011;22:324-32.

  18. I Don’t Understand My Lab Tests

  19. Blood Counts • White Blood Count • Platelets • Hematocrit (anemia)

  20. Kidney Tests • Urine protein/cr ratio • Blood creatinine

  21. Why Does Dr. Petri Emphasize Control of Risk Factors for Heart Disease?

  22. Cross section of the left anterior descending coronary artery. In this view, calcium (pink), vessel lumen (orange) and noncalcified plaque (green) have been identified

  23. What is an Antiphospholipid Antibody?What does it Do?

  24. Lupus anticoagulant = RVVT confirm • Anticardiolipin • Anti-beta2 Glycoprotein 1

  25. Kaplan-Meier Estimate of Remaining Free of Deep Venous Thrombosis Adjusted for Lupus Anticoagulant Cumulative S(t) Time Since SLE Diagnosis (y) Somers E, Magder LS, Petri M. J Rheumatol. 2002;29:2531–2536.

  26. I am tired all the time – isn’t it my lupus?

  27. Prevalence of Fibromyalgia 29.6% had 11 or more tender points Number of Patients

  28. How Do We Treat Fibromyalgia? • Tai Chi Stretching • Amitriptyline at bedtime • FDA-approved medications • Lyrica • Savella • Cymbalta

  29. Treatment Update

  30. Prednisone is Poison!

  31. Effect of Prednisone on Organ DamageAdjusting for Confounding by Indication Due to SLE Disease Activity Thamer M, et al. J Rheumatol. 2009;36:560–564.

  32. Prednisone Itself Increases the Risk of Cardiovascular Events 1. 3650 mg equals 10 mg/day for 1 year, or an equivalent cumulative exposure; 2. 1-3 years with 10 mg/day or an equivalent cumulative exposure; 3. 3-10 years with 10 mg/day or an equivalent cumulative exposure; 4.10+ years with 10 mg/day or an equivalent cumulative exposure; CVE=cardiovascular events Magder LS, Petri M. Am J Epidem 176:708-19, 2012.

  33. FLOAT TrialComparison of Oral Methylprednisolone and Intramuscular Triamcinolone Danowski A, et al. J Rheumatol. 2006;33:57-60.

  34. I have kidney lupus – what next?

  35. Treatments for Kidney Lupus • Mycophenolate (Cellcept) • ACE inhibitor or ARB • Hydroxychloroquine (Plaquenil) • Vitamin D

  36. Bad News: Mycophenolate Doesn’t Work For All • Cyclophosphamide • Tacrolimus (Prograf) • Rituximab (Rituxan)

  37. What are the New Therapies?

  38. Belimumab (Benlysta) • It blocks a growth factor (called BLyS or BAFF) that keeps autoimmune B cells alive • It is most likely to work if: • the lupus requires prednisone • the lupus is VERY active • there is anti-DNA AND low complement

  39. What Will be Available in the Future? • Anti-IL-6 • Anti-interferon alpha • Anti-BAFF/BLyS • Anti-CD22

  40. Articles on Lupus Center • At the Hopkins Arthritis Center main page (www.hopkinsarthritis.org) scroll down to the bottom of the page. • Click on the “Lupus Center” link on the bottom right hand side. • At the Lupus Center main page, click the “About the Center” link near the top left corner.

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