A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis
Loïc Guillevin,Jean-François Cordier,Franïois Lhote,Pascal Cohen,Bernard Jarrousse,Isabelle Royer,Philippe Lesavre,Christian Jacquot,Pascal Bindi,Philippe Bielefeld,Jean-Franïois Desson,Frédérick Détrée,Alain Dubois,Eric Hachulla,Bruno Hoen,Dominique Jacomy,Christian Seigneuric,Dominique Lauque,Marc Stern,Maité Longy-Boursier +19 more
TLDR
Pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality, however, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as Oral CYC.Abstract:
Objective. To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG).
Methods. Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued.
Results. Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02).
Conclusion. Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.read more
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A Randomized Trial of Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies
David Jayne,Niels Rasmussen,Konrad Andrassy,Paul A. Bacon,Jan Willem Cohen Tervaert,J. Dadoniene,Agneta Ekstrand,Gill Gaskin,Gina Gregorini,Kirsten de Groot,Wolfgang L. Gross,E. Christiaan Hagen,Eduardo Mirapeix,Erna Pettersson,Carl Siegert,Alberto Sinico,Vladimir Tesar,Kerstin Westman,Charles D. Pusey +18 more
TL;DR: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse, suggesting the duration of exposure to cycloph phosphamide may be safely reduced.
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Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel
Douglas A. Jabs,James T. Rosenbaum,C. Stephen Foster,Gary N. Holland,Glenn J. Jaffe,James S. Louie,Robert B. Nussenblatt,E. Richard Stiehm,Howard H. Tessler,Russell N. Van Gelder,Scott M. Whitcup,David E. Yocum +11 more
TL;DR: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care was formed in 1999 to provide recommendations for the use in the treatment of patients with ocular inflammatory disorders as discussed by the authors.
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EULAR Recommendations for the management of primary small and medium vessel vasculitis
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TL;DR: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
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EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.
Max Yates,Max Yates,Richard A. Watts,Ingeborg M. Bajema,Maria C. Cid,Bruno Crestani,Thomas H. Hauser,Bernhard Hellmich,Julia U Holle,Martin Laudien,Mark A. Little,Raashid Luqmani,Alfred Mahr,Peter A. Merkel,John Mills,Janice Mooney,Mårten Segelmark,Vladimir Tesar,Kerstin Westman,Augusto Vaglio,Nilüfer Yalçındağ,David Jayne,Chetan Mukhtyar +22 more
TL;DR: The 2009 European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated and 15 recommendations were developed, covering general aspects, such as attaining remission.
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Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis
Loïc Guillevin,Christian Pagnoux,Alexandre Karras,Chahéra Khouatra,Olivier Aumaître,Pascal Cohen,François Maurier,Olivier Decaux,Jacques Ninet,P. Gobert,Thomas Quemeneur,Claire Blanchard-Delaunay,Pascal Godmer,Xavier Puéchal,Pierre-Louis Carron,Pierre-Yves Hatron,Nicolas Limal,Mohamed Hamidou,Maize Ducret,Eric Daugas,Thomas Papo,Bernard Bonnotte,Alfred Mahr,Philippe Ravaud,Luc Mouthon +24 more
TL;DR: More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine, and the frequencies of severe adverse events were similar in the two groups.
References
More filters
Book ChapterDOI
Nonparametric Estimation from Incomplete Observations
Edward L. Kaplan,Paul Meier +1 more
TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Journal ArticleDOI
The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee.
Frederick Wolfe,Hugh A. Smythe,Muhammad B. Yunus,Robert M. Bennett,Claire Bombardier,Don L. Goldenberg,Peter Tugwell,Stephen M. Campbell,Micha Abeles,Patricia Clark,Adel G. Fam,Stephen J. Farber,Justus J. Fiechtner,C. Michael Franklin,Robert A. Gatter,Daniel Hamaty,James A. Lessard,Alan S. Lichtbroun,Alfonse T. Masi,Glenn A. McCain,W. John Reynolds,Thomas J. Romano,I. Jon Russell,Robert P. Sheon +23 more
TL;DR: Criteria for the classification of fibromyalgia are widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites, and no exclusions are made for the presence of concomitant radiographic or laboratory abnormalities.
Journal ArticleDOI
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.
Richard Peto,M.C. Pike,P. Armitage,N. E. Breslow,David Cox,S V Howard,N Mantel,Klim McPherson,Julian Peto,Pete Smith +9 more
TL;DR: Efficient methods of analysis of randomized clinical trials in which the authors wish to compare the duration of survival among different groups of patients are described.
Journal ArticleDOI
Wegener granulomatosis : an analysis of 158 patients
Gary S. Hoffman,Gail S. Kerr,Randi Y. Leavitt,Claire W. Hallahan,Robert S. Lebovics,William D. Travis,Menachem Rottem,Anthony S. Fauci +7 more
TL;DR: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids, and has led to increasing concerns about toxicity resulting from prolonged cycloph phosphamide therapy and has encouraged investigation of other therapeutic regimens.
Journal ArticleDOI
Wegener's granulomatosis: Prospective clinical and therapeutic experience with 85 patients for 21 years
TL;DR: It is shown that long-term remissions can be induced and maintained in an extremely high number of patients by the combination of daily cyclophosphamide and alternate-day prednisone therapy.
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