Title: Tuesday Clinical Case Conference
1Tuesday Clinical Case Conference
2Therapy of ANCA-Associated Small Vessel Vasculitis
3Introduction
- 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)
4Cyclophosphamide / Steroid
- Mainstay of treatment for both MPA and WG since
1980s - High rate of remission
- Significant morbidity
- Hemorragic cystitis
- Bladder cancer
- Myelodysplasia
- Infertility
- infection
5What are the approaches to maintaining remission
without CYC?
Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
6NORAM remission at 6 months
Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
7NORAM - relapses
Randomized Trial of Cya vs Mtx for Induction of
Remissioi nin early systemic ANCAAV_de
groot_ArthRheu_2005
8Minimizing 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?
9Which is better Oral or IV CYC?
- Guillevin L et al, Arthritis Rheum, 1997
- RCT of patients with WG
10CYC 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
11CYC Is IV pulse as effective as PO CYC?
12CYCLOPS Time to remission
13Cyclops Time to relapse
14Minimizing 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?
15CYCAZAREM trial
Jayne et al, NEJM, 3491, 2003
16CYCAZAREM - remission
Jayne et al, NEJM, 3491, 2003
17Time to first relapse
Jayne et al, NEJM, 3491, 2003
18CYCAZAREM renal recovery
Jayne et al, NEJM, 3491, 2003
19CYCAZAREM - 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
20Alternative 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
21Ongoing 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