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Raj Kiran Medapalli, MD, MPH. Nephrology Fellow May 19 th , 2009 Mount Sinai School of Medicine Division of Nephrology Journal Club
Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis The “CYCLOPS” Study European Vasculitis Study Group (EUVAS) Annals of Internal Medicine  19 May 2009   Journal Club by Raj Kiran Medapalli, MD
Outline ,[object Object],[object Object],[object Object],[object Object],[object Object]
Source: Brenner & Rector's The Kidney, 8 th  Edition.
Source: Jennette JC & Falk RJ. Small Vessel Vasculitis. NEJM. Nov 1997.  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Source: Falk RJ & Jennette JC. JASN. 1997. C-ANCA, anti-Proteinase 3 P-ANCA, anti-Myeloperoxidase Anti-neutrophil cytoplasmic antibodies
Source: Xiao H, et al.  Am J of Path. Jan 2007.
 
Cyclophosphamide (Cyc) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Source: UpToDate
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Source: UpToDate
Hoffman GS et al. Annals of Int Med. March 1992. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Hoffman GS et al. Annals of Int Med. March 1992.
Pulse Cyc in ANCA Vasculitis - EUVAS meta analysis  de Groot K et al. NDT 2001 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CYC vs MTX for Induction - EUVAS RCT (NORAM) de Groot K et al. Arth & Rheum Aug 2005 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Adjunctive Plasma Exchange or High-Dosage Solumedrol for Severe Renal Vasculitis. EUVAS RCT (MEPEX)   Jayne DRW et al. JASN 2007 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Azathioprine for Maintainance Rx. (CYCAZAREM) Jayne D, et al. NEJM 2003. EUVAS RCT. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
AZT vs. MTX for Maintenance Rx. FVSG RCT (WEGENT).   Pagnoux C, et al. NEJM 2008.  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis The “CYCLOPS” Study European Vasculitis Study Group (EUVAS) Annals of Internal Medicine  19 May 2009
Study Design ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Intervention Pulse (IV or PO) Cytoxan Daily PO Cytoxan Induction 15 mg/kg IV Q2wkly x 3 doses 2 mg/kg/d, until remission 15 mg/kg IV or 5 mg/kg PO on 3 consecutive days, q3wkly, until remission (physician discretion) Initial maintenance Continue above for 3 months 1.5 mg/kg/d for 3 months Max dose 1.2 g per pulse 200 mg/d Age 60-70 Reduce by 2.5 mg/kg per pulse Reduce by 25%  Age >70 Reduce by 5 mg/kg per pulse Reduce by 50%  Creat 3.4 to 5.7 Reduce by 2.5 mg/kg per pulse - CBC checks Day 0,10,14 Q wkly x 1 month, Q2wkly x 1 month, then monthly 3 - 4 x 10 9 /L - Withhold dose and resume at a dose reduced by 25 mg/d when WBC > 4 x 10 9 /L 2 - 3 x 10 9 /L Reduce dose by 20% 1 - 2 x 10 9 /L Reduce dose by 40%
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Birmingham Vasculitis Activity Scores (BVAS) ,[object Object],[object Object],[object Object],[object Object]
Birmingham Vasculitis Activity Scores (BVAS) ,[object Object],[object Object]
 
 
 
 
Time to Remission ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Main Outcome Parameters by Treatment Group ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Main Outcome Parameters by Treatment Group ,[object Object],[object Object],[object Object],[object Object],[object Object]
Renal Outcomes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Measures of disease activity ,[object Object],[object Object],[object Object],[object Object]
Cumulative dose ,[object Object],[object Object],[object Object],[object Object]
Adverse events ,[object Object],[object Object],[object Object],[object Object],[object Object]
Strengths of the study ,[object Object],[object Object],[object Object],[object Object],[object Object]
Weaknesses of the study ,[object Object],[object Object],[object Object],[object Object]
Conclusions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Ongoing trials at EUVAS ,[object Object],[object Object],[object Object],[object Object],[object Object]
Summary of Rx options for induction ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Rx options for maintainance ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
EUVAS Guidelines
Thank You.

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Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis (Journal Club)

  • 1. Raj Kiran Medapalli, MD, MPH. Nephrology Fellow May 19 th , 2009 Mount Sinai School of Medicine Division of Nephrology Journal Club
  • 2. Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis The “CYCLOPS” Study European Vasculitis Study Group (EUVAS) Annals of Internal Medicine 19 May 2009 Journal Club by Raj Kiran Medapalli, MD
  • 3.
  • 4. Source: Brenner & Rector's The Kidney, 8 th Edition.
  • 5.
  • 6. Source: Falk RJ & Jennette JC. JASN. 1997. C-ANCA, anti-Proteinase 3 P-ANCA, anti-Myeloperoxidase Anti-neutrophil cytoplasmic antibodies
  • 7. Source: Xiao H, et al. Am J of Path. Jan 2007.
  • 8.  
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 18. Pulse vs. Daily Oral Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis The “CYCLOPS” Study European Vasculitis Study Group (EUVAS) Annals of Internal Medicine 19 May 2009
  • 19.
  • 20. Intervention Pulse (IV or PO) Cytoxan Daily PO Cytoxan Induction 15 mg/kg IV Q2wkly x 3 doses 2 mg/kg/d, until remission 15 mg/kg IV or 5 mg/kg PO on 3 consecutive days, q3wkly, until remission (physician discretion) Initial maintenance Continue above for 3 months 1.5 mg/kg/d for 3 months Max dose 1.2 g per pulse 200 mg/d Age 60-70 Reduce by 2.5 mg/kg per pulse Reduce by 25% Age >70 Reduce by 5 mg/kg per pulse Reduce by 50% Creat 3.4 to 5.7 Reduce by 2.5 mg/kg per pulse - CBC checks Day 0,10,14 Q wkly x 1 month, Q2wkly x 1 month, then monthly 3 - 4 x 10 9 /L - Withhold dose and resume at a dose reduced by 25 mg/d when WBC > 4 x 10 9 /L 2 - 3 x 10 9 /L Reduce dose by 20% 1 - 2 x 10 9 /L Reduce dose by 40%
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.  
  • 26.  
  • 27.  
  • 28.  
  • 29.
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  • 33.
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  • 42.