SP0182 TREATMENT OF AAV
Authors: David Jayne
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> ANCA associated vasculitis is an autoimmune disease classified by clinical phenotype and serology. A genetic predisposition has been determined which differs between PR3-ANCA and MPO-ANCA patients. Experimental models have confirmed the pathogenicity of ANCA for certain aspects of pathology and have defined a role for alternative complement pathway activation but have failed to explain granuloma formation or gain insights into the origin of breakdown of tolerance. Therapy has emerged empirically to include the combination of high dose glucocorticoids and immunosuppression with B cell depletion, Rituximab, emerging as an alternative immunomodulator over the last 20 years. Studies have evaluated the role of Rituximab in induction, in refractory and relapsing disease and in the prevention of relapse and have explored the role of b biomarkers in monitoring therapy. AAV patients continue to suffer poor outcomes especially if renal, cardiac or gastrointestinal features are present at diagnosis. Adverse event rates remain high and the majority of patients pursue a relapsing course. Inhibition of the alternative complement component C5a is emerging as a new therapeutic opportunity. <h3>Objectives:</h3> To define the outcomes and predictors for adverse outcomes in AAV. To review recent clinical trial data in the context of established guideline statements and to discuss the treatment of more complex clinical scenarios. <h3>Methods:</h3> A description of current approaches to classification and subgrouping by severity. Review of recent clinical trial data and guidelines and application of learned knowledge to clinical scenarios. <h3>Conclusion:</h3> AAV remains a disease with poor outcomes. There is a need for further understanding of the barriers to early diagnosis and access to specialist care. Treatment decisions are now well supported by evidence from clinical trials. Rituximab has had a major influence on current management strategies and is leading to improved outcomes and reduced glucocorticoid exposure. Complement inhibition is a potential new therapy for AAV. <h3>References:</h3> [1] Jayne DR, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36-44. [2] De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR (senior author). Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:2461-2469. [3] Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18:2180-2188. [4] de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150:670-680. [5] Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR. Mycophenolate Mofetil vs Azathioprine for Remission Maintenance in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Trial. JAMA. 2010;304:2381-8. [6] Jones RB, Cohen Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR (senior author). Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363:211-220. [7] Jones RB, Furuta S, Cohen Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, Jayne DR. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015;74(6):1178-82 [8] Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalçindağ N, Jayne DR, Mukhtyar C. EULAR/ERA-EDTA recommendations for the management of ANCA associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94. [9] Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil ectoplasmic antibody associated vasculitis. JAMA. 2010 Dec 1;304(21):2381-8. <h3>Disclosure of Interests:</h3> David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda