Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis

Summary

This is a phase IV, single-center, randomized, placebo-controlled pilot study that will evaluate the efficacy of rituximab at inducing otolaryngologic remission in GPA patients with active otolaryngologic disease.

Timeline

Start

2015-12

Primary completion

2017-07

Completion

2017-07

Publications

• Background 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.
• Background Hogan SL, Falk RJ, Chin H, Cai J, Jennette CE, Jennette JC, Nachman PH. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med. 2005 Nov 1;143(9):621-31. doi: 10.7326/0003-4819-143-9-200511010-00005.
• Background Srouji IA, Andrews P, Edwards C, Lund VJ. General and rhinosinusitis-related quality of life in patients with Wegener's granulomatosis. Laryngoscope. 2006 Sep;116(9):1621-5. doi: 10.1097/01.mlg.0000230440.83375.4b.
• Background Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488-98. doi: 10.7326/0003-4819-116-6-488.
• Background 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.
• Background De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005 Aug;52(8):2461-9. doi: 10.1002/art.21142.
• Background 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.
• Background Jones RB, Furuta S, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh M, Westman K, Jayne DR; European Vasculitis Society (EUVAS). Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015 Jun;74(6):1178-82. doi: 10.1136/annrheumdis-2014-206404. Epub 2015 Mar 4.
• Background 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.
• Background Aries PM, Hellmich B, Voswinkel J, Both M, Nolle B, Holl-Ulrich K, Lamprecht P, Gross WL. Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis. 2006 Jul;65(7):853-8. doi: 10.1136/ard.2005.044420. Epub 2005 Nov 3.
• Background Seo P, Specks U, Keogh KA. Efficacy of rituximab in limited Wegener's granulomatosis with refractory granulomatous manifestations. J Rheumatol. 2008 Oct;35(10):2017-23. Epub 2008 Aug 1.
• Background Martinez Del Pero M, Chaudhry A, Jones RB, Sivasothy P, Jani P, Jayne D. B-cell depletion with rituximab for refractory head and neck Wegener's granulomatosis: a cohort study. Clin Otolaryngol. 2009 Aug;34(4):328-35. doi: 10.1111/j.1749-4486.2009.01968.x.
• Background Lally L, Lebovics RS, Huang WT, Spiera RF. Effectiveness of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis (Wegener's). Arthritis Care Res (Hoboken). 2014 Sep;66(9):1403-9. doi: 10.1002/acr.22311.
• Background Zhao Y, Odell E, Choong LM, Barone F, Fields P, Wilkins B, Tungekar FM, Patel P, Sanderson JD, Sangle S, D'Cruz D, Spencer J. Granulomatosis with polyangiitis involves sustained mucosal inflammation that is rich in B-cell survival factors and autoantigen. Rheumatology (Oxford). 2012 Sep;51(9):1580-6. doi: 10.1093/rheumatology/kes123. Epub 2012 May 23.
• Background Voswinkel J, Mueller A, Kraemer JA, Lamprecht P, Herlyn K, Holl-Ulrich K, Feller AC, Pitann S, Gause A, Gross WL. B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions. Ann Rheum Dis. 2006 Jul;65(7):859-64. doi: 10.1136/ard.2005.044909. Epub 2005 Nov 16.
• Background Thurner L, Muller A, Cerutti M, Martin T, Pasquali JL, Gross WL, Preuss KD, Pfreundschuh M, Voswinkel J. Wegener's granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin. J Autoimmun. 2011 Feb;36(1):87-90. doi: 10.1016/j.jaut.2010.09.002. Epub 2010 Oct 14.

Drugs

Indications