Etanercept for Wegener's Granulomatosis

Summary

This study will determine if the drug etanercept, also called Enbrel, is effective in producing and maintaining remission (reduction of disease symptoms) of Wegener's granulomatosis (WG). Etanercept blocks the action of tumor necrosis factor-alpha, a substance that may be involved in inflammatory conditions such as WG. Eight clinical centers around the United States will enroll 181 people who have WG. Patients will have an equal chance to receive either etanercept or placebo (inactive treatment). We will treat patients with standard medications for WG in addition to either etanercept or placebo. We will treat all patients with tapering doses of corticosteroids. After the patients' disease is controlled (in remission), we will reduce the dosages of the standard medications to lower the risk of side effects associated with these drugs. During the study, we will collect and save blood and tissues samples from patients and use the samples to address other medical questions, such as the cause of WG and factors that lead to disease progression.

Timeline

Start

2000-06

Primary completion

2003-03

Completion

2003-03

Publications

• Background Stone JH, Uhlfelder ML, Hellmann DB, Crook S, Bedocs NM, Hoffman GS. Etanercept combined with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum. 2001 May;44(5):1149-54. doi: 10.1002/1529-0131(200105)44:53.0.CO;2-F.
• Background Stone JH, Hoffman GS, Merkel PA, Min YI, Uhlfelder ML, Hellmann DB, Specks U, Allen NB, Davis JC, Spiera RF, Calabrese LH, Wigley FM, Maiden N, Valente RM, Niles JL, Fye KH, McCune JW, St Clair EW, Luqmani RA; International Network for the Study of the Systemic Vasculitides (INSSYS). A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum. 2001 Apr;44(4):912-20. doi: 10.1002/1529-0131(200104)44:43.0.CO;2-5.
• Background WGET Research Group. Design of the Wegener's Granulomatosis Etanercept Trial (WGET). Control Clin Trials. 2002 Aug;23(4):450-68. doi: 10.1016/s0197-2456(02)00209-x.
• Results Stone JH; Wegener's Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial. Arthritis Rheum. 2003 Aug;48(8):2299-309. doi: 10.1002/art.11075.
• Results Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC Jr, Hoffman GS, McCune WJ, St Clair EW, Specks U, Spiera R, Petri M, Stone JH; Wegener's Granulomatosis Etanercept Trial Research Group. 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. 2005 Apr 19;142(8):620-6. doi: 10.7326/0003-4819-142-8-200505030-00011.
• Results Stone JH, Rajapakse VN, Hoffman GS, Specks U, Merkel PA, Spiera RF, Davis JC, St Clair EW, McCune J, Ross S, Hitt BA, Veenstra TD, Conrads TP, Liotta LA, Petricoin EF 3rd; Wegener's Granulomatosis Etanercept Trial Research Group. A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis. Arthritis Rheum. 2005 Mar;52(3):902-10. doi: 10.1002/art.20938.
• Results Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, Davis JC, Ytterberg SR, St Clair EW, McCune WJ, Specks U, Allen NB, Luqmani RA, Stone JH; WGET Research Group. Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum. 2005 Jul;52(7):2168-78. doi: 10.1002/art.21117.
• Results Wung PK, Holbrook JT, Hoffman GS, Tibbs AK, Specks U, Min YI, Merkel PA, Spiera R, Davis JC, St Clair EW, McCune J, Ytterberg SR, Allen NB, Stone JH; WGET Research Group. Herpes zoster in immunocompromised patients: incidence, timing, and risk factors. Am J Med. 2005 Dec;118(12):1416. doi: 10.1016/j.amjmed.2005.06.012.
• Results Stone JH, Holbrook JT, Marriott MA, Tibbs AK, Sejismundo LP, Min YI, Specks U, Merkel PA, Spiera R, Davis JC, St Clair EW, McCune WJ, Ytterberg SR, Allen NB, Hoffman GS; Wegener's Granulomatosis Etanercept Trial Research Group. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum. 2006 May;54(5):1608-18. doi: 10.1002/art.21869.
• Clowse ME, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, Spiera RF, Davis JC Jr, McCune WJ, Ytterberg SR, St Clair EW, Allen NB, Specks U, Stone JH; WGET Research Group. Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care Res (Hoboken). 2011 Dec;63(12):1777-81. doi: 10.1002/acr.20605.

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