210 likes | 480 Views
Tuesday Clinical Case Conference. Zae Kim. Therapy of ANCA-Associated Small Vessel Vasculitis. Introduction. Best known induction therapy Cyclophosphamide / Steroid Search for alternative induction agent NORAM Minimizing the use of CYC Oral vs IV CyA - CYCLOPS
E N D
Tuesday Clinical Case Conference Zae Kim
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)
Mainstay of treatment for both MPA and WG since 1980s High rate of remission Significant morbidity Hemorragic cystitis Bladder cancer Myelodysplasia Infertility infection Cyclophosphamide / Steroid
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
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 • Minimizing the use of CYC • 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? • Guillevin L et al, Arthritis Rheum, 1997 • RCT of patients with WG
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; 16:2018-27
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?
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 • 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
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
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