FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 352:351-361 January 27, 2005 Number 4 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Bacon, P. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background The majority of patients with Wegener's granulomatosis have disease flares after conventional medications are tapered. There is no consistently safe, effective treatment for the maintenance of remission.

Methods We conducted a randomized, placebo-controlled trial at eight centers to evaluate etanercept for the maintenance of remission in 180 patients with Wegener's granulomatosis. The primary outcome was sustained remission, defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis of 0 for at least six months (scores can range from 0 to 67, with higher scores indicating more active disease). In addition to etanercept or placebo, patients received standard therapy (glucocorticoids plus cyclophosphamide or methotrexate). After remission, standard medications were tapered according to the protocol.

Results The mean follow-up for the overall cohort was 27 months. Of the 174 patients who could be evaluated, 126 (72.4 percent) had a sustained remission, but only 86 (49.4 percent) remained in remission for the remainder of the trial. There were no significant differences between the etanercept and control groups in the rates of sustained remission (69.7 percent vs. 75.3 percent, P=0.39), sustained periods of low-level disease activity (86.5 percent vs. 90.6 percent, P=0.32), or the time required to achieve those measures. Disease flares were common in both groups, with 118 flares in the etanercept group (23 severe and 95 limited) and 134 in the control group (25 severe and 109 limited). There was no significant difference between the etanercept and control groups in the relative risk of disease flares per 100 person-years of follow-up (0.89, P=0.54). During the study, 56.2 percent of patients in the etanercept group and 57.1 percent of those in the control group had at least one severe or life-threatening adverse event or died (P=0.90). Solid cancers developed in six patients in the etanercept group, as compared with none in the control group (P=0.01).

Conclusions Etanercept is not effective for the maintenance of remission in patients with Wegener's granulomatosis. Durable remissions were achieved in only a minority of the patients, and there was a high rate of treatment-related complications.

Source Information

As chairman of the WGET Research Group, Dr. John H. Stone accepts full responsibility for the integrity of the article.

Address reprint requests to Dr. John H. Stone at the Johns Hopkins Vasculitis Center, 5501 Hopkins Bayview Cir., JHAAC 1B.23, Baltimore, MD 21224, or at jstone{at}jhmi.edu.

Full Text of this Article

This article has been cited by other articles:

• Flossmann, O, Bacon, P, de Groot, K, Jayne, D, Rasmussen, N, Seo, P, Westman, K, Luqmani, R (2008). Development of comprehensive disease assessment in systemic vasculitis. Postgrad. Med. J. 84: 143-152 [Abstract] [Full Text]  
• Nouraei, S A R, Obholzer, R, Ind, P W, Salama, A D, Pusey, C D, Porter, F, Howard, D J, Sandhu, G S (2008). Results of endoscopic surgery and intralesional steroid therapy for airway compromise due to tracheobronchial Wegener's granulomatosis. Thorax 63: 49-52 [Abstract] [Full Text]  
• Wells, A. U., Latsi, P., McCune, W. J. (2007). Daily Cyclophosphamide for Scleroderma: Are Patients with the Most to Gain Underrepresented in this Trial?. Am. J. Respir. Crit. Care Med. 176: 952-953 [Full Text]  
• Finkielman, J. D., Merkel, P. A., Schroeder, D., Hoffman, G. S., Spiera, R., St. Clair, E. W., Davis, J. C. Jr., McCune, W. J., Lears, A. K., Ytterberg, S. R., Hummel, A. M., Viss, M. A., Peikert, T., Stone, J. H., Specks, U., for the WGET Research Group, (2007). Antiproteinase 3 Antineutrophil Cytoplasmic Antibodies and Disease Activity in Wegener Granulomatosis. ANN INTERN MED 147: 611-619 [Abstract] [Full Text]  
• LAMPRECHT, P., TILL, A., STEINMANN, J., ARIES, P. M., GROSS, W. L. (2007). Current State of Biologicals in the Management of Systemic Vasculitis. Ann. N. Y. Acad. Sci. 1110: 261-270 [Abstract] [Full Text]  
• Bosch, X., Guilabert, A., Espinosa, G., Mirapeix, E. (2007). Treatment of Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Systematic Review. JAMA 298: 655-669 [Abstract] [Full Text]  
• Robinson, M. R., Korman, B. D., Korman, N. J. (2007). Combination Immunosuppressive Therapies: The Promise and the Peril. Arch Dermatol 143: 1053-1057 [Abstract] [Full Text]  
• Jayne, D. (2007). Leflunomide versus methotrexate in Wegener's granulomatosis. Rheumatology (Oxford) 46: 1047-1048 [Full Text]  
• Zandi, M. S, Coles, A. J (2007). Notes on the kidney and its diseases for the neurologist. J. Neurol. Neurosurg. Psychiatry 78: 444-449 [Abstract] [Full Text]  
• Hellmich, B., Flossmann, O., Gross, W. L, Bacon, P., Willem Cohen-Tervaert, J., Guillevin, L., Jayne, D., Mahr, A., Merkel, P. A, Raspe, H., Scott, D. G I, Witter, J., Yazici, H., Luqmani, R. A, on behalf of the European Vasculitis Study Group, (2007). EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 66: 605-617 [Abstract] [Full Text]  
• Sangle, S. R, Hughes, G. R V, D'Cruz, D. P (2007). Infliximab in patients with systemic vasculitis that is difficult to treat: poor outcome and significant adverse effects. Ann Rheum Dis 66: 564-565 [Full Text]  
• Flossmann, O., Bacon, P., de Groot, K., Jayne, D., Rasmussen, N., Seo, P., Westman, K., Luqmani, R. (2007). Development of comprehensive disease assessment in systemic vasculitis. Ann Rheum Dis 66: 283-292 [Abstract] [Full Text]  
• Daikeler, T., Kotter, I., Bocelli Tyndall, C., Apperley, J., Attarbaschi, A., Guardiola, P., Gratwohl, A., Jantunen, E., Marmont, A., Porretto, F., Musso, M., Maurer, B., Rinaldi, N., Saccardi, R., Tyndall, A., for the EBMT Autoimmune Diseases Working Party, (2007). Haematopoietic stem cell transplantation for vasculitis including Behcet's disease and polychondritis: a retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature. Ann Rheum Dis 66: 202-207 [Abstract] [Full Text]  
• Johnston, S. L (2007). Biologic therapies: what and when?. J. Clin. Pathol. 60: 8-17 [Abstract] [Full Text]  
• Andrews, J., Mason, J. C. (2007). Takayasu's arteritis--recent advances in imaging offer promise. Rheumatology (Oxford) 46: 6-15 [Abstract] [Full Text]  
• Yazici, Y, Yazici, H (2007). A survey of inclusion of the time element when reporting adverse effects in randomised controlled trials of cyclo-oxygenase-2 and tumour necrosis factor {alpha} inhibitors. Ann Rheum Dis 66: 124-127 [Abstract] [Full Text]  
• Hellmann, D. B., Imboden, J. B. (2006). Update in Rheumatology. ANN INTERN MED 145: 834-838 [Full Text]  
• Callegari, P. E., Schaible, T. F., Boscia, J. A. (2006). Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis.. JAMA 296: 2202-2202 [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Emery, P, Keystone, E C, Schiff, M H, van Riel, P L C M, Weinblatt, M E, Weisman, M H (2006). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 65: iii2-iii15 [Full Text]  
• Huugen, D., Cohen Tervaert, J. W., Heeringa, P. (2006). TNF-{alpha} Bioactivity-Inhibiting Therapy in ANCA-Associated Vasculitis: Clinical and Experimental Considerations. CJASN 1: 1100-1107 [Abstract] [Full Text]  
• Chou, R C, Henson, J W, Tian, D, Hedley-Whyte, E T, Reginato, A M (2006). Successful treatment of rheumatoid meningitis with cyclophosphamide but not infliximab.. Ann Rheum Dis 65: 1114-1116 [Full Text]  
• Bongartz, T., Sutton, A. J., Sweeting, M. J., Buchan, I., Matteson, E. L., Montori, V. (2006). Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.. JAMA 295: 2275-2285 [Abstract] [Full Text]  
• Hermann, J, Reittner, P, Scarpatetti, M, Graninger, W (2006). Successful treatment of meningeal involvement in Wegener's granulomatosis with infliximab.. Ann Rheum Dis 65: 691-692 [Full Text]  
• Kettritz, R., Choi, M., Salanova, B., Wellner, M., Rolle, S., Luft, F. C. (2006). Fever-Like Temperatures Affect Neutrophil NF-{kappa}B Signaling, Apoptosis, and ANCA-Antigen Expression. J. Am. Soc. Nephrol. 17: 1345-1353 [Abstract] [Full Text]  
• Morgan, M. D., Harper, L., Williams, J., Savage, C. (2006). Anti-Neutrophil Cytoplasm-Associated Glomerulonephritis. J. Am. Soc. Nephrol. 17: 1224-1234 [Abstract] [Full Text]  
• Feldmann, M., Pusey, C. D. (2006). Is There a Role for TNF-{alpha} in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases. J. Am. Soc. Nephrol. 17: 1243-1252 [Abstract] [Full Text]  
• Foster, R, Rosenthal, E, Marques, S, Vounotrypidis, P, Sangle, S, D'Cruz, D (2006). Primary systemic vasculitis: treatment of difficult cases. Lupus 15: 143-147 [Abstract]  
• Thickett, D. R., Richter, A. G., Nathani, N., Perkins, G. D., Harper, L. (2006). Pulmonary manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Rheumatology (Oxford) 45: 261-268 [Full Text]  
• Frankel, S. K., Cosgrove, G. P., Fischer, A., Meehan, R. T., Brown, K. K. (2006). Update in the diagnosis and management of pulmonary vasculitis.. Chest 129: 452-465 [Abstract] [Full Text]  
• Keogh, K. A., Ytterberg, S. R., Fervenza, F. C., Carlson, K. A., Schroeder, D. R., Specks, U. (2006). Rituximab for Refractory Wegener's Granulomatosis: Report of a Prospective, Open-Label Pilot Trial. Am. J. Respir. Crit. Care Med. 173: 180-187 [Abstract] [Full Text]  
• Brown, K. K. (2006). Pulmonary vasculitis.. Proc Am Thorac Soc 3: 48-57 [Abstract] [Full Text]  
• Little, M. A., Bhangal, G., Smyth, C. L., Nakada, M. T., Cook, H. T., Nourshargh, S., Pusey, C. D. (2006). Therapeutic Effect of Anti-TNF-{alpha} Antibodies in an Experimental Model of Anti-Neutrophil Cytoplasm Antibody-Associated Systemic Vasculitis. J. Am. Soc. Nephrol. 17: 160-169 [Abstract] [Full Text]  
• GORONZY, J. J., HENEL, G., SAWAI, H., SINGH, K., LEE, E. B., PRYSHCHEP, S., WEYAND, C. M. (2005). Costimulatory Pathways in Rheumatoid Synovitis and T-Cell Senescence. Ann. N. Y. Acad. Sci. 1062: 182-194 [Abstract] [Full Text]  
• Hogan, S. L., Falk, R. J., Chin, H., Cai, J., Jennette, C. E., Jennette, J. C., Nachman, P. H. (2005). Predictors of Relapse and Treatment Resistance in Antineutrophil Cytoplasmic Antibody-Associated Small-Vessel Vasculitis. ANN INTERN MED 143: 621-631 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Bijlsma, J W J, Dougados, M, Emery, P, Keystone, E C, Klareskog, L, Mease, P J (2005). Updated consensus statement on biological agents, specifically tumour necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005. Ann Rheum Dis 64: iv2-iv14 [Full Text]  
• Mukhtyar, C, Luqmani, R (2005). Current state of tumour necrosis factor {alpha} blockade in Wegener's granulomatosis. Ann Rheum Dis 64: iv31-iv36 [Abstract] [Full Text]  
• Pagnoux, C, Guillevin, L (2005). Cardiac involvement in small and medium-sized vessel vasculitides. Lupus 14: 718-722 [Abstract]  
• Watts, R., Harper, L., Jayne, D., Levy, J., Pusey, C., Savage, C., Scott, D. G. I., Williams, J. (2005). Translational research in autoimmunity: aims of therapy in vasculitis. Rheumatology (Oxford) 44: 573-576 [Full Text]  
• Merkel, P. A., Lo, G. H., Holbrook, J. T., Tibbs, A. K., Allen, N. B., Davis, J. C. Jr, Hoffman, G. S., McCune, W. J., St. Clair, E. W., Specks, U., Spiera, R., Petri, M., Stone, J. H., for The Wegener's Granulomatosis Etanercept Trial, (2005). Brief Communication: High Incidence of Venous Thrombotic Events among Patients with Wegener Granulomatosis: The Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. ANN INTERN MED 142: 620-626 [Abstract] [Full Text]  
• Frankel, S K, Cosgrove, G P, Brown, K K (2005). Small vessel vasculitis of the lung. Chronic Respiratory Disease 2: 75-84 [Abstract]  
• Ballinger, S., Wiedermann, B. (2005). Therapy for Wegener's Granulomatosis. AAP Grand Rounds 13: 45-45 [Full Text]  
• (2005). Etanercept Is Not Effective for Wegener Granulomatosis. Journal Watch Dermatology 2005: 6-6 [Full Text]