Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis

Summary

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common type of small blood vessel inflammation in adults. ANCA-associated vasculitis includes Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Rituximab is a man-made antibody used to treat certain types of cancer. The purpose of this study is to determine the effectiveness of rituximab in treating patients with WG and MPA. Study hypothesis: Rituximab is not inferior to conventional therapy in its ability to induce disease remission by Month 6.

Timeline

Start

2005-01

Primary completion

2008-12

Completion

2010-01

Publications

• Background Zarin DA. Participant-level data and the new frontier in trial transparency. N Engl J Med. 2013 Aug 1;369(5):468-9. doi: 10.1056/NEJMe1307268. No abstract available.
• Results Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.
• Results Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277.
• Results Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Viviano L, Ding L, Sejismundo LP, Mieras K, Ikle D, Jepson B, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2013 Sep;65(9):2441-9. doi: 10.1002/art.38044.
• Results Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Ikle D, Kallenberg CG, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013 Aug;72(8):1342-50. doi: 10.1136/annrheumdis-2012-201981. Epub 2012 Sep 12.
• Results Nasrallah M, Pouliot Y, Hartmann B, Dunn P, Thomson E, Wiser J, Butte AJ. Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment. Arthritis Res Ther. 2015 Sep 21;17(1):262. doi: 10.1186/s13075-015-0778-z.
• Results Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Ding L, Ikle D, Villareal M, Lim N, Brunetta P, Fervenza FC, Monach PA, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids. Arthritis Rheumatol. 2015 Jun;67(6):1629-36. doi: 10.1002/art.39104.
• Results Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Viviano L, Ding L, Ikle D, Villarreal M, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Rituximab for the treatment of relapses in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2014 Nov;66(11):3151-9. doi: 10.1002/art.38788.
• Berti A, Hillion S, Hummel AM, Son YM, Chriti N, Peikert T, Carmona EM, Abdulahad WH, Heeringa P, Harris KM, St Clair EW, Brunetta P, Fervenza FC, Langford CA, Kallenberg CG, Merkel PA, Monach PA, Seo P, Spiera RF, Stone JH, Grandi G, Sun J, Pers JO, Specks U, Cornec D; RAVE-ITN Research Group. Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis. JCI Insight. 2021 Nov 22;6(22):e150999. doi: 10.1172/jci.insight.150999.
• Kronbichler A, Leierer J, Shin JI, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CGM, St Clair EW, Brunetta P, Fervenza FC, Geetha D, Keogh KA, Monach PA, Ytterberg SR, Mayer G, Specks U, Stone JH; RAVE-ITN Research Group. Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2019 Nov;71(11):1888-1893. doi: 10.1002/art.41017. Epub 2019 Sep 25.
• Wallace ZS, Miloslavsky EM, Cascino M, Unizony SH, Lu N, Hoffman GS, Kallenberg CGM, Langford CA, Merkel PA, Monach PA, Seo P, Spiera R, St Clair EW, Specks U, Brunetta P, Choi HK, Stone JH. Effect of Disease Activity, Glucocorticoid Exposure, and Rituximab on Body Composition During Induction Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1004-1010. doi: 10.1002/acr.23099.
• Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CM, St Clair EW, Ikle D, Tchao NK, Ding L, Brunetta P, Choi HK, Monach PA, Fervenza F, Stone JH, Specks U; RAVE-ITN Research Group. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis. 2016 Jun;75(6):1166-9. doi: 10.1136/annrheumdis-2015-208073. Epub 2015 Nov 30.

Drugs

Indications