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What’s New in SLE? A Ten Step Program

What’s New in SLE? A Ten Step Program. Michelle Petri MD MPH Johns Hopkins University School of Medicine. 1. Classification Criteria Help in Everyday Practice. SLICC* Classification Criteria.

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What’s New in SLE? A Ten Step Program

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  1. What’s New in SLE?A Ten Step Program Michelle Petri MD MPH Johns Hopkins University School of Medicine

  2. 1. Classification Criteria Help in Everyday Practice

  3. SLICC* Classification Criteria SLICC has recommended that BOTH the revised ACR criteria AND the new SLICC classification criteria be used *Systemic Lupus International Collaborating Clinics At least 1 clinical + at least 1 immunologic criterion (for a total of 4) OR lupus nephritis by biopsy Petri M et al. Arthritis Rheum. 2012;64:2677-2686.

  4. SLICC Revision of ACR Classification Criteria Petri M et al. Arthritis Rheum. 2012;64:2677-2686.

  5. SLICC Revision of ACR Classification Criteria Petri M et al. Arthritis Rheum. 2012;64:2677-2686.

  6. 2. More Good Reasons to Avoid Prednisone

  7. A Prednisone Dose of 6 mg or More Increases Organ Damage by 50% Adjusted for confounding by indication due to SLE disease activity ThamerM et al. J Rheumatol. 2009;36:560-564.

  8. Prednisone Itself Increases the Risk of Cardiovascular Events Magder LS, Petri M. Am J Epidemol. 2012;176:708-719.

  9. 3. Non-immunosuppressive Immunomodulators Can Control Mild-Moderate SLE, Helping to Avoid Steroids 1. Petri M. Lupus. 1996;5(Suppl 1):S16-S22. 2. Petri M et al. Arthritis Rheum. 2013;65:1865-1871 . 3 Petri M et al. Arthritis Rheum. 2002;46:1820-1829. 4. Lai Z-W et al. Arthritis Rheum. 2012;64:2937-2946. • Hydroxychloroquine1 • Vitamin D2 • Prasterone (synthetic dihydroepiandrosterone, • or DHEA)3 • N-acetylcysteine4

  10. Hydroxychloroquine as Background Therapy

  11. Hydroxychloroquine for Lupus Nephritis • Continuing hydroxychloroquine improves complete response rates with mycophenolatemofetil KasitanonN et al. Lupus2006;15:366-370.

  12. Increasing 25-Hydroxy Vitamin D Modestly Helps Disease Activity and Urine Protein/CR Model allowing slope to differ before and after 40 ng/mL SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Petri M et al. Arthritis Rheum. 2013;65:1865-1871.

  13. 20-Unit Increase in 25-Hydroxy Vitamin D • 13% decrease in odds of having a PGA score of 1 or more • 21% decrease in odds of having a SLEDAI score of 5 or more • 15% decrease in odds of having a urine pr/cr > 0.5 Petri, et al. Arthritis Rheum 2013;65:1865-71

  14. Vitamin D May Have Cardiovascular and Hematologic Benefits Targher G et al. SeminThrombHemostasis. 2012;38:114-124.

  15. Vitamin D Reduced Thrombosis in Some Clinical Studies 1. Beer TM et al. Br J Haematol. 2006;135:392-394. 2. Brøndum-Jacobsen P et al. J ThrombHaemost . 2013;11:423-431. 3. Grant WB. Am J Hematol. 2010;85:908. 4. Lindqvist PG et al. J ThrombHaemost . 2009;7:605-610. 5. Kojima G et al. Stroke. 2012;43:2163-2167. 6. Shanker J et al. Coron Artery Dis. 2011;22:324-332. • Cancer RCT: calcitriol+docetaxel vs. docetaxel (P=0.01)1 • General population lowest tertile of vitamin D: • 37% (CI 15-64%) increased rate of VTE2 • Higher rates of VTE in African-Americans3 • VTE are seasonal: highest risk in winter; sunbathing reduces rise of VTE by 30%4 • Honolulu Heart Program: Low vitamin D predicted 34-year incident • stroke in Japanese-American men. HR 1.22 (CI 1.02-1.47), P=0.0385 • Asian Indian cohort: mean vitamin D lower in CAD P=0.0366

  16. DHEA (Prasterone) 200 mg Daily • NOT FDA-approved • In women with disease activity, reduction in • prednisone to ≤7.5 mg/day achieved in 51% vs. • 29% on placebo (P=0.03).1 • In women with disease activity, improvement or • stabilization achieved in 58.5% vs. 44.5% on • placebo (P=0.017)2 1. Petri M et al. Arthritis Rheum. 2002;46:1820-1829. 2. Petri M et al. Arthritis Rheum. 2004;50:2858-2868.

  17. Prasterone Reduces SLE Flares

  18. DHEA and Bone Density • Prasterone provides mild protection against bone loss • At month 18 with 200 mg vs. 100 mg: Dose-dependent increase in spine BMD (P=0.02) Sanchez-Guerrero J et al. J Rheumatol. 2008;35:1567-1575.

  19. N-acetylcysteine Lai Z-W et al. Arthritis Rheum. 2012;64:2937-2946. • Blocks mTOR in T cells • At 2.4 and 4.8 g, it reduced SLEDAI at 1, 2, 3 and 4 • months • But 4.8 g caused reversible nausea in 33%

  20. 4. MycophenolateMofetil: The Good, the Bad, . . . . .

  21. Lupus Nephritis Induction Therapy:MMF = IV Cyclophosphamide Therapy • Not FDA-indicated for SLE 1. Appel GB, et al. J Am Soc Nephrol.2009;20(5):1103-1112; Ginzler EM, et al. Arthritis Rheum. 2010;62(1):211-221; Tornatore KM, et al. J ClinPharmacol 2011;51:1213-22. 2. FDA Warning label for MMF. • In non-Caucasians, MMF is superior • In renal transplant literature: • African-Americans 3 grams • Caucasians 2 grams • New issue: MMF interferes with oral contraceptive dosing • “It is recommended that oral contraceptives are coadministered with MMF with caution and additional birth control methods be considered”2

  22. Lupus Nephritis Maintenance Therapy :MMF is Superior to Azathioprine N=227 Time to treatment failure Time to renal flare Dooley MA, et al. N Engl J Med. 2011;365:1886-95. • Not FDA-indicated for SLE

  23. Lupus Nephritis: Other Options • Leflunomide, tacrolimus, and rituximab are not FDA-indicated for SLE 1. Navarra S, et al. Lancet. 2011;377(9767):721-31; 2. Dooley MA, et al. ACR/AHCP annual meeting. November 4-9, 2011;Chicago, IL; 3. Tam LS, et al. Lupus. 2004;13:601-4; 4. Wang HY, et al. Lupus. 2008;17(638-44); 5. Tam LD, et al. Ann Rheum Dis. 2006;65:417-8; 6. Yap DY et al. Nephrology. 2012; 10.1111/j.1440-1797.2012.01574.x; 7. Li X, et al. Nephrol Dial Transplant. 2011; doi: 10.1093/ndt/gfr484; 8. Cortes-Hernandez J, et al; Nephrol Dial Transplant. 2010;25(12):3939-489. 9. Lanata CM, et al. Lupus. 2010:19(8):935-40. 10. Szeto CC, et al. Rheumatology. 2008;47(11):1678-81; 11. Rovin BH, et al. Arth Rheum. 2012;doi: 10.1002/art.34359. 12. Chen W, et al. Lupus. 2012:21(7):944-952. • Belimumab • Not studied specifically in SLE patients with active nephritis1,2 • Leflunomide • For mild-to-moderate SLE disease3 • Induction therapy for renal flare4,5 • Tacrolimus • Consider in MMF-resistant or partial response patients, alone or in combination6-9,12 • Approved for treatment of LN in Japan • For severe nephritis (Class IV/V)6,10 • Rituximab • LUNAR trial was negative11

  24. Time to Remission and Relapse After Rituximab Treatment and MMF Maintenance Condon MB, et al. Ann Rheum Dis. 2013;72:1280-6.

  25. 5. Better Understanding of Belimumab

  26. Belimumab Multivariate Analysis Characteristics associated with greater treatment effect (p<0.1) • SELENA SLEDAI score: ≥10 (vs ≤9) • Complement: low C3/C4 (vs normal) • Steroid use: greater (vs no/less) Characteristics not associated with treatment effect (p>0.1) • Study • Region • Race van Vollenhoven, et al. Ann Rheum Dis, 2012. [April Epub ahead of print, doi: 10.1136/annrheumdis-2011-200937].

  27. Low C/Anti-dsDNA + Subgroup:SRI Response Rate over 52 Weeks van Vollenhoven RF, et al. Presented at EULAR 2011; May 25-28, 2011; London, UK

  28. SELENA SLEDAI Organ Improvement (Week 52)a Improvement = decrease in SS score within an organ domain Manzi S, et al. Ann Rheum Dis, 2012. [May Epub ahead of print, doi: 10.1136/annrheumdis-2011-200831].

  29. Belimumab vs Placebo: Severe Flares Cervera R, et al. Presented at EULAR 2011: Annual European Congress of Rheumatology; May 25–28, 2011; London, UK

  30. 6. Don’t Forget New Information on Common Drugs

  31. http://www.medpagetoday.com/PainManagement/PainManagement/44253 (accessed on 3/12/2014)

  32. New Data on PPIs

  33. Proton Pump Inhibitors and Fractures http://www.fda.gov/drugs/resourcesforyou/healthprofessionals/ucm221672.htm (accessed on 3/12/2014)

  34. http://www.news-medical.net/news/20130711/Research-shows-proton-pump-inhibitors-may-cause-cardiovascular-problems.aspx (accessed on 3/12/2014)

  35. 7. Progress on Coronary Artery Disease

  36. Coronary Artery Disease in SLE • Substantial increased risk that cannot be completely explained by traditional Framingham risk factors1 • Hospitalization for acute myocardial infarction (AMI) 2.3 times higher in SLE2 • Risk of cardiovascular events is 2.66 times higher in SLE vs Framingham cohort3 1. Esdaile JM, et al. Arthritis Rheum 2001;44: 2331-7; 2. Ward MM. Arthritis Rheum. 1999;42(2):338-46; 3. Magder LS, Petri M. Am J Epidemiol. In press.

  37. How Can We Detect Cardiovascular Disease Early in SLE? 1. Kiani AN et al. J Rheumatol. 2008;35:1300-1306. 2. Maksimowicz-McKinnon K et al. J Rheumatol. 2006;33:2458-2463. 3. Kiani AN et al. J Rheumatol. 2010;37:579-584. • Coronary calcium CT1 • Carotid duplex2 • In the FUTURE, techniques such as coronary CTA can • detect early noncalcified coronary plaques3

  38. Cross section of the left anterior descending coronary artery. In this view, calcium (pink), vessel lumen (orange) and noncalcified plaque (green) have been identified. Coronary Calcium CT Kiani AN et al. J Rheumatol. 2010;37:579-584.

  39. Prevention of CAD in SLE

  40. Atorvastatin Did Not Change Petri M et al. Ann Rheum Dis2010;70:760-765. Schanberg LE et al. Arthritis Rheum. 2012;64:285-296. Coronary calcium Carotid intima media thickness Carotid plaque

  41. Can We Reduce Cardiovascular Risk? • Assess traditional cardiovascular risk factors and treat to target • Hypertension • Obesity • Hyperlipidemia • Smoking • Sedentary Lifestyle • Statin did NOT reduce progression in mice3 nor in two clinical trials: • Adult1 • Pediatric2 • Mycophenolate: slowed progression in mice3 and transplant patients4 • Prednisone > 10 mg increases CV event risk5 1. Petri MA, et al. Ann Rheum Dis. 2011;70(5):760-5; 2. Schanberg LE, et al. Arthtiris Rheum. 2012;64(1):285-96; 3. van Leuven SI, et al. Ann Rheum Dis. 2012 ;71(3):408-14; 4. Gibson WT, Hayden MR. Ann N Y Acad Sci. 2007 Sep;1110:209-21; 5. Magder L, et al. Am J Epidemiol. 2012; in press.

  42. 8. Prevention of Thrombosis in SLE: Are We There Yet?

  43. Venous Thrombosis in SLE Cumulative S(t) Time Since SLE Diagnosis (years) Somers E, Magder LS, Petri M. J Rheumatol. 2002;29:2531–2536.

  44. Hydroxychloroquine Prevents Thrombosis in SLE Petri M. CurrRheumatol Reports 2010:13:77-80

  45. 9. Don’t Make Fibromyalgia WORSE(It’s Bad Enough as it is!)

  46. Treating Pain and Fatigue: Tai Chi 12 weeks 79% of tai chi group vs 39% of control had clinically meaningful improvement* (P=0.0001) 24 weeks 82% of tai chi vs 53% control had clinically meaningful improvement (P=0.009) FIQ=fibromyalgia impact questionnaire; *”clinically meaningful” change in FIQ = 8.1 points Wang C, et al. N Engl J Med.2010;363(8):743-754.

  47. Fatigue 1. Tench CM et al. Rheumatology. 2000;39(11):1249–54; 2. Wang B, et al. J Rheumatol. 1998;25(5):892-5; 3. Gladman D, et al. J Rheum. 1997;24:2145-9; 4. Bruce IN, et al. Arthritis Rheum. 1998; 41(suppl.9):S333; 5. Carr FN, et al. ACR/AHCP annual meeting. November 4-9, 2011;Chicago, IL. • Among most common complaints in lupus patients (50-80% of patients)1 • Chronic fatigue does not correlate with disease activity2 • Highly correlated with fibromyalgia, pain, depression, sleep abnormalities, poor quality of life2-5 • Associated with reduced physical fitness6

  48. Exercise for SLE-related Fatigue Tench CM, et al. Rheumatology. 2003;42:1050-54.

  49. “Overall, 11 of 22 patients completing a 90-day treatment with naltrexone had a robust response with 41% improvement on the Revised Fibromyalgia Impact Questionnaire.” http://www.obgynnews.com/single-view/naltrexone-hyperbaric-oxygen-show-promise-for-fibromyalgia/f2d53e04496f14b0294457246f645741.html (accessed on 3/12/2014)

  50. 10. Headaches Aren’t Usually Due to Lupus

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