User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.

Primary tabs

Houssiau, Frédéric [UCL] Vasconcelos, Carlos D'Cruz, David Sebastiani, Gian Domenico Garrido Ed, Enrique de Ramon Depresseux, Geneviève [UCL] Cosyns, Jean-Pierre [UCL] Cervera, Ricard

OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2002
Journal information "Arthritis & Rheumatism" - Vol. 46, no. 8, p. 2121-2131 (2002)
Peer reviewed yes
Publisher John Wiley & Sons, Inc. (Hoboken)
issn 0004-3591
e-issn 1529-0131
Publication status Publié
Affiliations UCL - MD/MINT - Département de médecine interne
UCL - MD/MNOP - Département de morphologie normale et pathologique
UCL - (SLuc) Service de rhumatologie
UCL - (SLuc) Service d'anatomie pathologique
MESH Subject Adolescent ; Adult ; Aged ; Azathioprine - therapeutic use ; Cyclophosphamide - administration & dosage - therapeutic use ; Dose-Response Relationship, Drug ; Female ; Humans ; Immunosuppressive Agents - administration & dosage - therapeutic use ; Injections, Intravenous ; Kidney Function Tests ; Lupus Nephritis - blood - drug therapy - pathology ; Male ; Middle Aged ; Remission Induction ; Single-Blind Method ; Treatment Failure
Links
  1. Austin Howard A., Klippel John H., Balow James E., Le Riche Nicole G.H., Steinberg Alfred D., Plotz Paul H., Decker John L., Therapy of Lupus Nephritis, 10.1056/nejm198603063141004
  2. Boumpas D.T., Austin H.A., Balow J.E., Vaughan E.M., Yarboro C.H., Klippel J.H., Steinberg A.D., Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis, 10.1016/0140-6736(92)92292-n
  3. Gourley Mark F., Methylprednisolone and Cyclophosphamide, Alone or in Combination, in Patients with Lupus Nephritis : A Randomized, Controlled Trial, 10.7326/0003-4819-125-7-199610010-00003
  4. Illei Gabor G., Austin Howard A., Crane Marianna, Collins Lee, Gourley Mark F., Yarboro Cheryl H., Vaughan Ellen M., Kuroiwa Takashi, Danning Carol L., Steinberg Alfred D., Klippel John H., Balow James E., Boumpas Dimitrios T., Combination Therapy with Pulse Cyclophosphamide plus Pulse Methylprednisolone Improves Long-Term Renal Outcome without Adding Toxicity in Patients with Lupus Nephritis, 10.7326/0003-4819-135-4-200108210-00009
  5. Urowitz, Rheum Dis Clin North Am, 19, 263 (1993)
  6. Ponticelli C., Treatment of lupus nephritis-the advantages of a flexible approach, 10.1093/ndt/12.10.2057
  7. Bansal Vinod K., Beto Judith A., Treatment of lupus nephritis: A meta-analysis of clinical trials, 10.1016/s0272-6386(97)90029-9
  8. Boumpas Dimitrios T., Risk for Sustained Amenorrhea in Patients with Systemic Lupus Erythematosus Receiving Intermittent Pulse Cyclophosphamide Therapy, 10.7326/0003-4819-119-5-199309010-00003
  9. Houssiau F.A., D'Cruz D.P., Haga H.-J., Hughes G.R.V., Short Course of Weekly Low-Dose Intravenous Pulse Cyclophosphamide in the Treatment of Lupus Nephritis: A Preliminary Study, 10.1177/096120339100100106
  10. D'Cruz, Clin Exp Rheumatol, 15, 275 (1997)
  11. Haga H J, D'Cruz D, Asherson R, Hughes G R, Short term effects of intravenous pulses of cyclophosphamide in the treatment of connective tissue disease crisis., 10.1136/ard.51.7.885
  12. Tan Eng M., Cohen Alan S., Fries James F., Masi Alfonse T., Mcshane Dennis J., Rothfield Naomi F., Schaller Jane Green, Talal Norman, Winchester Robert J., The 1982 revised criteria for the classification of systemic lupus erythematosus : REVISED CRITERIA FOR SLE, 10.1002/art.1780251101
  13. Morel-Maroger, Adv Nephrol Necker Hosp, 6, 79 (1976)
  14. Treasure T., MacRae K. D, Minimisation: the platinum standard for trials?, 10.1136/bmj.317.7155.362
  15. Vitali, Clin Exp Rheumatol, 10, 541 (1992)
  16. Balow, Kidney Int, 49, S88 (1996)
  17. Dooley Mary Anne, , Hogan Susan, Jennette Charles, Falk Ronald, Cyclophosphamide therapy for lupus nephritis: Poor renal survival in black Americans, 10.1038/ki.1997.162
  18. Bardsley-Elliot Anne, Noble Stuart, Foster Rachel H., Mycophenolate Mofetil : A Review of its Use in the Management of Solid Organ Transplantation, 10.2165/00063030-199912050-00005
  19. , Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection, 10.1016/s0140-6736(95)92534-1
  20. Kobashigawa Jon, Miller Leslie, Renlund Dale, Mentzer Robert, Alderman Edwin, Bourge Robert, Costanzo Maria, Eisen Howard, Dureau Georges, Ratkovec Ranae, Hummel Manfred, Ipe David, Johnson Jay, Keogh Anne, Mamelok Richard, Mancini Donna, Smart Frank, Valantine Hannah, A RANDOMIZED ACTIVE-CONTROLLED TRIAL OF MYCOPHENOLATE MOFETIL IN HEART TRANSPLANT RECIPIENTS1 : , 10.1097/00007890-199808270-00016
  21. Chan Tak Mao, Li Fu Keung, Tang Colin S.O., Wong Raymond W.S., Fang Guo Xiang, Ji Yu Lian, Lau Chak Sing, Wong Andrew K.M., Tong Matthew K.L., Chan Kwok Wah, Lai Kar Neng, Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis, 10.1056/nejm200010193431604
  22. Dawisha, J Rheumatol, 23, 273 (1996)
  23. McCune, J Rheumatol, 23, 212 (1996)
Bibliographic reference Houssiau, Frédéric ; Vasconcelos, Carlos ; D'Cruz, David ; Sebastiani, Gian Domenico ; Garrido Ed, Enrique de Ramon ; et. al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.. In: Arthritis & Rheumatism, Vol. 46, no. 8, p. 2121-2131 (2002)
Permanent URL http://hdl.handle.net/2078.1/9229