Transcript ANCA vasculitis

Tuesday Clinical Case
Conference
Zae Kim
Therapy of ANCA-Associated
Small Vessel Vasculitis
Introduction
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Best known induction therapy
• Cyclophosphamide / Steroid
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Search for alternative induction agent
• NORAM
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Minimizing the use of CYC
• Oral vs IV CyA - CYCLOPS
• CYCAZAREM (cyclophosphamide vs azathioprine
for early remission phase of vasculitis)
Cyclophosphamide / Steroid
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Mainstay of treatment
for both MPA and WG
since 1980s
 High rate of remission
 Significant morbidity
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Hemorragic cystitis
Bladder cancer
Myelodysplasia
Infertility
infection
What are the approaches to
maintaining remission without CYC?
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NORAM
Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005
NORAM – remission at 6 months
Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005
NORAM - relapses
Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005
Minimizing exposure to CYC
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Minimizing the use of CYC
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Induction
• Oral vs IV CyA - CYCLOPS
•
Maintenance
• CYCAZAREM (cyclophosphamide vs azathioprine
for early remission phase of vasculitis)
• MMF?
Which is better: Oral or IV CYC?
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Guillevin L et al, Arthritis Rheum, 1997
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RCT of patients with WG
Group A (CYC IV)
n = 27
Group B (CYC PO)
n = 23
Initial remission
89%
78%
Infectious side
effect
Relapse
41%
70%
(p < 0.05)
60%
13%
(p = 0.02)
CYC: oral vs pulse IV, meta
analysis
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Meta-analysis
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11 non-randomized studies
N = 202 patients
Pulse vs daily oral Cya
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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; 16:2018-27
CYC: Is IV pulse as effective as PO
CYC?
CYCLOPS – Time to remission
Cyclops – Time to relapse
Minimizing exposure to CYC
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Minimizing the use of CYC
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Induction
• Oral vs IV CyA - CYCLOPS
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Maintenance
• CYCAZAREM (cyclophosphamide vs azathioprine
for early remission phase of vasculitis)
• MMF?
CYCAZAREM trial
Jayne et al, NEJM, 349;1, 2003
CYCAZAREM - remission
Jayne et al, NEJM, 349;1, 2003
Time to first relapse
Jayne et al, NEJM, 349;1, 2003
CYCAZAREM – renal recovery
Jayne et al, NEJM, 349;1, 2003
CYCAZAREM - conclusion
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No difference in relapse rate
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Only predictor of relapse was
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CTX (14%) vs AZA (15%)
MPA (8%) vs WG (18%)
No difference in serious adverse events
Alternative to AZA as maintenance
therapy
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MTx / Leflunomide
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Metzler et al, Rheumatology 2007
• 55 patients with generalized WG
• Study terminated early 2/2
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higher rate of relapse in MTx group
high rate of adverse event in Leflunomide
IMPROVE by EUVAS
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MMF vs AZA
Ongoing trials at EUVAS
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Length of long-term immunosuppressive therapy?
• REMAIN
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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
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MMF as remission agent?
• IMPROVE
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Clearance of nasal carriage of Staph Aureus
with mupirocin in WG
• MUPIBAC