Clinical Trials in Vasculitis

Jennette JC et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65:1–11. This article provides a framework for the current nomenclature system of systemic vasculitis.

Hagen EC et al. Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay standardization. Kidney Int. 1998;53:743–53.

Sable-Fourtassou R et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005;143:632–8.

Jayne D et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44.

Jayne D. Update on the European vasculitis study group trials. Curr Opin Rheumatol. 2001;13(1):48–55.

The Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med. 2005;352:351–61.

Hellmich B et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007;66:605–17.

Lyons PA et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367:214–23. A landmark paper confirming the genetic association of ANCA-associated vasculitis with ANCA specificity.

Pierrot-Deseilligny Despujol C, Pouchot J, Pagnoux C, Coste J, Guillevin L. Predictors at diagnosis of a first Wegener’s granulomatosis relapse after obtaining complete remission. Rheumatology (Oxford). 2010;49:2181–90.

Franssen CF et al. Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Kidney Int. 2000;57:2195–206.

Furuta S, Jayne DRW. Antineutrophil cytoplasm antibody-associated vasculitis: recent developments. Kidney Int. 2013;84:244–9.

Xiao H et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110:955–63.

Sanders J-SF, Huitma MG, Kallenberg CGM, Stegeman CA. Plasma levels of soluble interleukin 2 receptor, soluble CD30, interleukin 10 and B cell activator of the tumour necrosis factor family during follow-up in vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies: associations with disease activity and relapse. Ann Rheum Dis. 2006;65:1484–9.

Abdulahad WH, Kallenberg CGM, Limburg PC, Stegeman CA. Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009;60:2830–8.

Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CGM. Skewed distribution of Th17 lymphocytes in patients with Wegener’s granulomatosis in remission. Arthritis Rheum. 2008;58:2196–205.

Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol. 2007;170:52–64.

Schreiber A et al. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol. 2009;20:289–98.

Flossmann O et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488–94.

De Groot K et al. Pulse versus daily oral cyclophosphamide for induction of remission. Ann Intern Med. 2009;150:670–80.

Harper L et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012;71:955–60.

Westman K, Flossmann O, Gregorini G. The long-term outcomes of systemic vasculitis. Nephrol Dial Transplant. 2015;30:i60–6.

Stone JH, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis—NEJM. N Engl J Med. 2010. doi: 10.1056/NEJMoa0909169 . This study established the non-inferiority of rituximab to cyclophosphamide in induction of remission in AAV patients.

Jones RB et al. Rituximab versus cyclophosphamide in ANCA-Associated Renal Vasculitis. N Engl J Med. 2010;363:211–20. This study established the non-inferiority of rituximab to cyclophosphamide in induction of remission in AAV patients with severe renal disease.

Specks U et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369:417–27.

Jones RB, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015;1–5. doi: 10.1136/annrheumdis-2014-206404 .

De Groot K et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:2461–9.

Faurschou M et al. Brief report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64:3472–7.

Draibe J et al. Use of mycophenolate in ANCA-associated renal vasculitis: 13 years of experience at a university hospital. Nephrol Dial Transplant. 2015;30 Suppl 1:i132–7.

Silva F et al. Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement—a prospective, open-label pilot trial. Clin J Am Soc Nephrol. 2010;5:445–53.

Jones R, et al. A randomized trial of mycophenolate mofetil versus cyclophosphamide for remission induction of ANCA-associated vasculitis: ‘“MYCYC”’. On behalf of the European vasculitis study group. Presse Med. 2013;678–69.

Walsh, M. et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials 14,73 (2013).

ChemoCentryx, Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis (CLEAR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/NCT02222155 . NLM identifier: NCT 02222155

Walsh M et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013;84:397–402.

Fortin PM, Tejani AM, Bassett K, Musini VM. Intravenous immunoglobulin as adjuvant therapy for Wegener’s granulomatosis. Cochrane Datab Syst Rev. 2013;1:CD007057.

Jayne DRW et al. Intravenous immunoglobulin for ANCA‐associated systemic vasculitis with persistent disease activity. QJM. 2000;93:433–9.

Hoffman GS et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–98.

Mukhtyar C et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68:310–7.

Randomised trial of prolonged remission-maintenance therapy in systemic vasculitis, REMAIN. www.vasculitis.org/trials/active/REMAIN . at http://www.vasculitis.org/images/documents/remain jan 2006.pdf .

Walsh M et al. Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis. Clin J Am Soc Nephrol. 2014;9:1571–6.

Guillevin L et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371:1771–80. This study established the efficacy of rituximab in ANCA-associated vasculitis remission maintenance.

Rituximab vasculitis maintenance study (RITAZAREM). ClinicalTrials.gov NCT0169726.

Alberici, F. et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology 1–8 (2014). doi: 10.1093/rheumatology/keu452 .

Assistance Publique - Hôpitaux de Paris, Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis (MAINRITSAN 2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/ NCT01731561 . NLM identifier: NCT NCT01731561

Assistance Publique - Hôpitaux de Paris, Comparison Between a Long Term and a Conventional Maintenance Treatment With Rituximab (MAINRITSAN3). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/NCT02433522 . NLM identifier: NCT NCT02433522

Pagnoux C et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359:2790–803.

Hiemstra TF et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis. JAMA. 2011;304:2381–8.

Stegeman CA, Tervaert JWC, Jong PEDE, Kallenberg CGM. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. N Engl J Med. 1996;335:16–20.

Walsh, M., Merkel, P. & Mahr, A. The effects of duration of glucocorticoid therapy on relapse rate in anti-neutrophil cytoplasm antibody associated vasculitis: a meta-analysis. Arthritis Care Res. 2010;62:1166–1173.

University of South Florida, The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach (TAPIR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/NCT01933724 . NLM identifier: NCT01933724

Chiba University, Low-dose Glucocorticoid Vasculitis Induction Study (LoVAS). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/ NCT02198248 . NLM identifier: Identifier: NCT02198248.

Guillevin L et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore). 1996;75:17–28.

Groh M et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss) (EGPA) consensus task force recommendations for evaluation and management. Eur J Intern Med. 2015;26:545–53.

Ribi C et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum. 2008;58:586–94.

Cohen P et al. Churg-Strauss syndrome with poor-prognosis factors: a prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum. 2007;57:686–93.

Mohammad AJ et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Ann Rheum Dis. 2014. doi: 10.1136/annrheumdis-2014-206095 .

Jakiela B et al. Increased production of IL-5 and dominant Th2-type response in airways of Churg–Strauss syndrome patients. Rheumatology. 2012;51:1887–93.

Bekker P, Jayne D, Brukfeld A. CCX168, an orally administered C5aR inhibitor for treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis - ACR Meeting Abstracts. 2014 ACR/ARHP Annual Meeting. 2014. at http://acrabstracts.org/abstract/ccx168-an-orally-administered-c5ar-inhibitor-for-treatment-of-patients-with-antineutrophil-cytoplasmic-antibody-associated-vasculitis/ .

Human Genome Sciences Inc., a GSK Company,Belimumab in Remission of VASculitis (BREVAS), In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/ NCT01663623 . NLM identifier: ClinicalTrials.gov Identifier: NCT01663623

University of South Florida, Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (ABROGATE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2016 Apr 07]. Available from: https://clinicaltrials.gov/ct2/show/ NCT02108860 . NLM identifier:: NCT02108860