1 / 49

Treatment of LN

Treatment of LN. An European perspective Frédéric A. HOUSSIAU Department of Rheumatology Cliniques universitaires Saint-Luc LOUVAIN Medical School XXXV Congreso de la SEN Malaga, October 9-12, 2005. High-dose IV CYC. Remission rate : 80% Relapse rate: 35% ESRD: 5-10%

olesia
Download Presentation

Treatment of LN

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Treatment of LN An European perspective Frédéric A. HOUSSIAU Department of Rheumatology Cliniques universitaires Saint-Luc LOUVAIN Medical School XXXV Congreso de la SEN Malaga, October 9-12, 2005

  2. High-dose IV CYC Remission rate : 80% Relapse rate: 35% ESRD: 5-10% Side-effects: +++

  3. Why European initiatives ? European LN patients differ from American LN patients Ethnic background !

  4. Prognostic factors Afro-American race Poor socio-economic status Severe clinical onset High CI, AI Uncontrolled hypertension Renal relapse Non-compliance Poor initial response to therapy UCL

  5. Why European initiatives ? European LN patients differ from American LN patients Less severe disease at baseline?

  6. LN : Bedside classification 5 56 % 2 % 4 3 Serum albumin (g/dl) 2 1 26 % 16 % 0 0.4 1.3 1.6 0.7 1 1.9 2.2 Serumcreatinine(mg/dl) Louvain LN Cohort (1985-2002) UCL

  7. B o u m p a s 8 0 E L N T 6 0 Percentage of patients 4 0 2 0 0 C r e a t > 1 . 3 m g / d l P r o t e i n u r i a > 3 . 5 g / d ELNT - Patients UCL

  8. The changing picture of LN Study from Heidelberg Fiehn C. et al. Ann Rheum Dis 2003; 62: 435-9

  9. The cyclophosphamide saga Towards lower doses of IV CYC ? Euro-Lupus Group 1990-2000

  10. Euro-Lupus Nephritis Trial 90 SLE patients biopsy-proven proliferative GN (III, IV, Vc/d) ≥ 500 mg daily proteinuria not treated with ISD UCL

  11. Euro-Lupus Nephritis Trial 750 mg IV methylprednisolone pulse d1, d2 and d3 0.5 mg/kg/d oral prednisolone 1 month (1 mg/kg/d in severe cases) tapered down to 7.5 mg/d at 6 months UCL

  12. MINIMISATION LD IV CYC HD IV CYC NIH-like regime 6 monthly pulses 2 quarterly pulses start AZA w 44 6 pulses 500 mg q2 weeks start AZA w 12 Euro-Lupus Nephritis Trial UCL

  13. ELNT - Baseline data UCL Houssiau et al., Arthritis Rheum, 2002

  14. 100 90 80 70 60 50 0 0 12 24 36 48 60 ELNT - Treatment failure LD HD Free of Failure (%) HD LD HR: 0.79 (CIs: 0.30-2.14) Follow-up (months) UCL Houssiau et al., Arthritis Rheum, 2002

  15. HD HD 1.4 4.0 LD LD 3.5 1.3 3.0 1.2 2.5 Serum Creatinine (mg/dl) 1.1 24-hour Proteinuria (g) 2.0 1.0 1.5 0.9 1.0 0.5 0.8 0 0 12 12 0 3 6 0 3 6 Months Months ELNT - Kinetics p < 0.005 for « repeated measures » analyses (ANOVA) p > 0.05 for « between groups » comparisons UCL Houssiau et al., Arthritis Rheum, 2002

  16. 4 2 1 0 0 4 . 0 9 0 3 . 8 8 0 3 . 6 7 0 3 . 4 3 . 2 6 0 3 . 0 5 0 2 . 8 0 0 12 0 3 6 Months ELNT - Kinetics . Serum C 3 (mg/dl) Serum Albumin (g/dl) HD HD LD LD 12 0 3 6 Months p < 0.005 for « repeated measures » analyses (ANOVA) p > 0.05 for « between groups » comparisons UCL Houssiau et al., Arthritis Rheum, 2002

  17. HD HD LD LD 8 4 0 7 3 5 6 3 0 Prednisolone (mg/day) 2 5 5 ECLAM Score 4 2 0 3 1 5 2 1 0 1 5 0 3 6 12 0 3 6 12 0 0 M o n t h s M o n t h s ELNT - Kinetics p < 0.005 for « repeated measures » analyses (ANOVA) p > 0.05 for « between groups » comparisons UCL Houssiau et al., Arthritis Rheum, 2002

  18. Baseline Followup 20 p = 0.013 p = 0.001 15 Activity index (mean ± SEM) 10 5 0 HD group LD group Pathology UCL

  19. Pathology UCL

  20. ELNT - Severe infections UCL Houssiau et al., Arthritis Rheum, 2002; 46: 2121-2131

  21. ELNT - Long term follow-up 100 80 60 LD 40 20 HD 0 p = 0.34 HR: 0.35 (0.04-3.37) Free of ESRD (%) [46] [45] [44] [42] [37] [27] [22] [8] HD [44] [43] [42] [40] [35] [31] [19] [6] LD 0 1 2 3 4 5 6 7 8 Follow-up (years) UCL Houssiau et al., Arthritis Rheum, 2004; 50: 3934-3940

  22. ELNT - Long term follow-up Mean (± SD) follow-up: 70 ± 17 months Houssiau et al., A&R, 2004; 50: 3934

  23. ELNT - Baseline pronostic factors UCL Houssiau et al., A&R, 2004; 50: 3934

  24. An understudied prognostic factors Does the initial response to immunosuppressive therapy predict long-term renal outcome in LN ? UCL

  25. Lack of prompt response is a poor prognostic factor Adjustment for baseline creatinine by ANCOVA p = 0.018 5 ANOVA p = 0.0003 p = 0.011 4 3 2 1 0 Good renal outcome Houssiau et al., A&R, 2004; 50: 3934 24h proteinuria (g) Month 6 Month 3 Baseline UCL Poor renal outcome

  26. Multivariate analysis of predictors of good long-term renal outcome Houssiau et al., Arthritis Rheum, 2004; 50: 3934-3940 UCL

  27. Lesson from the ELNT A short- course of low-dose IV CYC might be enough in the induction phase 6 x 500 mg q2w Euro-Lupus regimen UCL

  28. EURO-LUPUS regimen ADVANTAGES 30 minutes drip CYC infusion no need for hyperhydration no hospital stay low cost no need to monitor nadir WBC less side-effects UCL

  29. ELNT - Caveats Not blinded Not strict NIH regimen Not an equivalence study Less severe LN patients Few Blacks UCL

  30. The cyclophosphamide saga Gorman C et al., Rheumatology 2005; 44: 398-401

  31. Low-dose is superior to high-dose IV CYC for LN Pro: 45 % Con: 50 % No idea: 5 % Gorman C et al., Rheumatology 2005; 44: 398-401

  32. HD LD 100 80 LD 60 Free of renal flare (%) HD 40 AZA LD AZA 20 HD HR: 0.90 (CIs: 0.40-2.04) 0 0 12 24 36 48 60 Follow-up (months) ELNT - Renal flares UCL Houssiau et al., Arthritis Rheum, 2002

  33. Mycophenolate mofetil A new star twinckling in the sky

  34. Can MMF replace oral CYC for induction ? Group 1 MMF: 2g/d for 6 months 1g/d for 6 months Group 2 CPM: 2.5 mg/kg/d for 6 months AZA: 1.5 mg/kg/d for 6 months Chan et al. , NEJM 2000; 343: 1156

  35. Chan et al. , NEJM 2000; 343: 1156

  36. Can MMF replace oral CYC for induction ? After one year, all patients were on AZA More early relapses in MMF group Additional patients were given higher MMF doses for longer periods Long-term analysis on 32 MMF and 30 CYC patients Chan et al., JASN 2005; 16: 1076

  37. Chan’s study - Caveat Changes in treatment regimen over time (more MMF; longer period)

  38. LN : Mycophenolate mofetil MMF less toxic than CYC No evidence so far than MMF is less efficacious than CYC Pregnancy issue Superior to AZA for maintenance ?

  39. MAINTAIN NEPHRITIS TRIAL INDUCTION OF REMISSION Glucocorticoids IV CYC mini-pulses : 6 x 500 mg q2 weeks MAINTENANCE OF REMISSION AZA MMF houssiau@ruma.ucl.ac.be UCL

  40. MAINTAIN NEPHRITIS TRIAL MMF is superior to AZA as remission-maintaining therapy for lupus glomerulonephritis Hypothesis Study design Multi-center, randomized, unblinded, controlled trial 1ry endpoint Time to renal flare houssiau@ruma.ucl.ac.be

  41. Is MMF superior to AZA ?ASPREVA nephritis trial INDUCTION 6 months MAINTENANCE Up to 3 years MMF MMF Response? AZA Yes Re-randomise IVC Randomise No - exit study

  42. Induction: A reasonable choice GC 3 x IV MP 1000 mg 0.5 mg/kg/d pred. taper by 2.5 mg q2w + CYC6 x 500 q2w 6 x 750-1000 qm oral for 12w MMF 2-3 g/d or

  43. Advantages of IV CYC Optimal adherence to therapy Low cost

  44. LN - Treatment costs « Good value for money… »

  45. Maintenance: A reasonable choice Quarterly IV high-dose CYC (NIH regimen) Low-dose GC (5-7.5 mg/d pred.) + or AZA2.5 mg/kg/d MMF2 g/d UCL

  46. Optimal care for lupus patients BLOOD PRESSURE CONTROL (DBP ≤ 80 mm Hg) MINIMIZE PROTEINURIA (ACEI + DIURETICS) TREATMENT OF DYSLIPIDAEMIA STATINS! PREVENTION OF GC-INDUCED BONE LOSS IMMUNISATIONS STOP SMOKING UCL

  47. Asanuma Y. et al.

  48. Frequently Unanswered Questions Consensus on definitions Induction/maintenance: myth ? IS treatment: for how long ? Cost/effectiveness analysis Membranous vs proliferative GN Refractory cases

  49. You should not kill the patient to save their kidneys Steward Cameron

More Related