Background: Mycophenolate mofetil (MMF) is an immune suppressive initially introduced for the prevention of solid organ allograft rejection that is increasingly used in autoimmune conditions, including vasculitis. Methods: This retrospective study evaluated the efficacy and tolerability of MMF in 51 sequential patients with anti-neutrophil cytoplasm antibodies-associated systemic vasculitis (AASV) treated in a single centre between 2001 and 2004. Results: The mean age was 54 years and median disease duration was 36 months. A mean of 3.5 systems were involved and the previous median exposure to cyclophosphamide was 9 g. MMF was administered either as remission maintenance therapy (29/51, 56.9%) or as treatment for active disease (22/51, 43.1%). The mean duration of MMF therapy was 20 months and the mean MMF dose during the first year was 1.6 g/day. 14/29 (48.3%) of those receiving MMF for remission maintenance therapy eventually relapsed with a mean time to relapse of 14 months. Of those receiving MMF for relapsing disease, 3 failed to respond to therapy while the rest achieved remission by 3.9 months. However, 9 of these subsequently flared; mean time to disease flare was also 14 months. MMF was withdrawn in 28 patients (54.9%) because of treatment inefficacy in 21, severe adverse events in 5 and intolerance in 2. Of the 51 treated, 36 (70.6%) experienced at least 1 side effect, namely infections in 24, gastrointestinal side effects in 12 and psychological events in 6 patients. Conclusions: We have observed varying efficacy of MMF in AASV, with over 50% of patients with relapsing disease achieving remission and marked falls in concomitant steroid doses. However, longer follow-up indicates a subsequent relapse rate of over 50% that may be associated with low MMF dosing.

Keywords:
Mycophenolate mofetil, Systemic vasculitis, Tolerability, Efficacy
1.
Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH, Plaisance M, Pusey CD, Jayne DR: Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 2003;41:776–784.
2.
Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349:36–44.
3.
Langford CA, Talar-Williams C, Barron KS, Sneller MC: Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener’s granulomatosis: extended follow-up and rate of relapse. Am J Med 2003;114:463–469.
4.
Reinhold-Keller E, Fink CO, Herlyn K, Gross WL, De Groot K: High rate of renal relapse in 71 patients with Wegener’s granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum 2002;47:326–332.
5.
Nowack R, Gobel U, Klooker P, Hergesell O, Andrassy K, van der Woude FJ: Mycophenolate mofetil for maintenance therapy of Wegener’s granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol 1999;10:1965–1971.
6.
Langford CA, Talar-Williams C, Sneller MC: Mycophenolate mofetil for remission maintenance in the treatment of Wegener’s granulomatosis. Arthritis Rheum 2004;51:278–283.
7.
Bijl M, Horst G, Bootsma H, Limburg PC, Kallenberg CG: Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk. Ann Rheum Dis 2003;62:534–539.
8.
Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, Lau CS, Wong AK, Tong MK, Chan KW, Lai KN: Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000;343:1156–1162.
9.
Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al: Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187–192.
10.
Schmitt WH, Jayne DRW, van der Woode FJ, for the European Vasculitis Study Group (EUVAS): Mycophenolate mofetil (MMF) vs. azathioprine (AZA) for the maintenance of remission in ANCA-associated vasculitis: The IMPROVE Protocol. Kidney Blood Press Res 2003;26:295.
11.
Stassen P, Cohen Tervaert JW, Stegeman CA: Induction of remission in active ANCA-associated vasculitis with mycophenolate mofetil. Kidney Blood Press Res 2003;26:292.
12.
Sanquer S, Breil M, Baron C, Dahmane D, Astier A, Lang P: Trough blood concentrations in long-term treatment with mycophenolate mofetil. Lancet 1998;351:1557.
13.
Neumann I, Haidinger M, Jager H, Grutzmacher H, Griesmacher A, Muller MM, Bayer PM, Meisl FT: Pharmacokinetics of mycophenolate mofetil in patients with autoimmune diseases compared renal transplant recipients. J Am Soc Nephrol 2003;14:721–727.
14.
Dooley MA, Cosio FG, Nachman PH, Falkenhain ME, Hogan SL, Falk RJ, Hebert LA: Mycophenolate mofetil therapy in lupus nephritis: clinical observations. J Am Soc Nephrol 1999;10:833–839.
15.
Choi MJ, Eustace JA, Gimenez LF, Atta MG, Scheel PJ, Sothinathan R, Briggs WA: Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098–1114.
16.
Meier-Kriesche HU, Steffen BJ, Hochberg AM, Gordon RD, Liebman MN, Morris JA, Kaplan B: Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration. Transplantation 2003;75:1341–1346.
17.
Maes B, Oellerich M, Ceuppens JL, Armstrong VW, Evenepoel P, Kuypers D, Messiaen T, Shipkova M, Wieland E, Vanrenterghem Y: A new acute inflammatory syndrome related to the introduction of mycophenolate mofetil in patients with Wegener’s granulomatosis. Nephrol Dial Transplant 2002;17:923–926.
18.
Riskalla MM, Somers EC, Fatica RA, McCune WJ: Tolerability of mycophenolate mofetil in patients with systemic lupus erythematosus. J Rheumatol 2003;30:1508–1512.
19.
Halloran P, Mathew T, Tomlanovich S, Groth C, Hooftman L, Barker C: Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups. Transplantation 1997;63:39–47.
20.
Booth A, Harper L, Hammad T, Bacon P, Griffith M, Levy J, Savage C, Pusey C, Jayne D: Prospective study of TNF-α blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol 2004;15:717–721.
21.
Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group: Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 2005;352:351–361.
22.
Keogh KA, Wylam ME, Stone JH, Specks U: Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005;52:262–268.
23.
Lockwood CM, Thiru S, Isaacs JD, Hale G, Waldmann H: Long-term remission of intractable systemic vasculitis with monoclonal antibody therapy. Lancet 1993;341:1620–1622.
24.
Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grunke M, Peter HH, Kalden JR, Gobel U, Drexler JM, Hotta O, Nowack R, Van Der Woude FJ: 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol 2003;14:440–447.
© 2006 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.