Tuesday Clinical Case Conference

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Tuesday Clinical Case Conference

• Zae Kim

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Therapy of ANCA-Associated Small Vessel Vasculitis
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Introduction

• Best known induction therapy
• Cyclophosphamide / Steroid
• Search for alternative induction agent
• NORAM
• Minimizing the use of CYC
• Oral vs IV CyA - CYCLOPS
• CYCAZAREM (cyclophosphamide vs azathioprine for
  early remission phase of vasculitis)

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Cyclophosphamide / Steroid

• Mainstay of treatment for both MPA and WG since
  1980s
• High rate of remission
• Significant morbidity
• Hemorragic cystitis
• Bladder cancer
• Myelodysplasia
• Infertility
• infection

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What are the approaches to maintaining remission
without CYC?

• NORAM

Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
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NORAM remission at 6 months
Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
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NORAM - relapses
Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
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Minimizing exposure to CYC

• Minimizing the use of CYC
• Induction
• Oral vs IV CyA - CYCLOPS
• Maintenance
• CYCAZAREM (cyclophosphamide vs azathioprine for
  early remission phase of vasculitis)
• MMF?

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Which is better Oral or IV CYC?

• Guillevin L et al, Arthritis Rheum, 1997
• RCT of patients with WG

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CYC oral vs pulse IV, meta analysis

• Meta-analysis
• 11 non-randomized studies
• N 202 patients
• Pulse vs daily oral Cya
• No difference in death / ESRD / remission
• More relapses OR 1.79 (CI 0.85-3.75)
• Less infections RR 0.45
• Lower dose 17 g vs. 35 g
• not statistically significant

K de Groot et al. Nephrol Dial Transplant 2001
162018-27
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CYC Is IV pulse as effective as PO CYC?
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CYCLOPS Time to remission
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Cyclops Time to relapse
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Minimizing exposure to CYC

• Minimizing the use of CYC
• Induction
• Oral vs IV CyA - CYCLOPS
• Maintenance
• CYCAZAREM (cyclophosphamide vs azathioprine for
  early remission phase of vasculitis)
• MMF?

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CYCAZAREM trial
Jayne et al, NEJM, 3491, 2003
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CYCAZAREM - remission
Jayne et al, NEJM, 3491, 2003
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Time to first relapse
Jayne et al, NEJM, 3491, 2003
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CYCAZAREM renal recovery
Jayne et al, NEJM, 3491, 2003
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CYCAZAREM - conclusion

• No difference in relapse rate
• CTX (14) vs AZA (15)
• Only predictor of relapse was
• MPA (8) vs WG (18)
• No difference in serious adverse events

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Alternative to AZA as maintenance therapy

• MTx / Leflunomide
• Metzler et al, Rheumatology 2007
• 55 patients with generalized WG
• Study terminated early 2/2
• higher rate of relapse in MTx group
• high rate of adverse event in Leflunomide
• IMPROVE by EUVAS
• MMF vs AZA

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Ongoing trials at EUVAS

• Length of long-term immunosuppressive therapy?
• REMAIN
• long-term low dose immunosuppression versus
  treatment withdrawal for renal vasculitis
• Alternative induction agent?
• MYCYC (Randomized clinical trial of MMF vs CYC
  for remission induction in ANCA-AV)
• RITUXVAS
• MMF as remission agent?
• IMPROVE
• Clearance of nasal carriage of Staph Aureus with
  mupirocin in WG
• MUPIBAC