SP0044 WIN: VASCULITIS MAINTENANCE TREATMENT
Authors: Raashid Luqmani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Cyclophosphamide and more recently rituximab have transformed the outcome for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), resulting in survival in most cases. However, patients are at risk of frequent relapses, low grade grumbling disease, drug toxicity and worsening co-morbidity. Historically, prolonged courses of cyclophosphamide (used for both induction and maintenance) increased the risk of malignancy (especially bladder cancer). More limited use of cyclophosphamide, or the use of other agents including rituximab or methotrexate (for milder forms) offer safer but still effective options. The high relapse risk in AAV (especially in GPA) means that maintenance therapy is necessary but there is uncertainty over the most effective, safe long term choice. Maintenance RTX (fixed dose at fixed intervals of 4-6 months) is superior to azathioprine, but it is not clear if combination maintenance is superior to RTX alone. Long term side effects of RTX include hypogammaglobulinaemia and potential for reactivation of JC virus. Reducing the glucocorticoid burden in AAV remains a challenge. We still do not know how long to continue therapy in AAV. Two recent studies provide conflicting opinion on the duration of maintenance therapy using azathioprine on risk of future relapse. The use of low doses of rituximab has recently explored in AAV: in thyroid eye disease, 100mg rituximab is effective. Less frequent dose intervals, as used in rheumatoid arthritis, will not control AAV. Future studies could address optimal long term management of patients with AAV, in order to improve their quality of survival and well-being. <h3>Objectives:</h3> To assess the risk of relapse of vasculitis and to review the evidence for the use, effectiveness and toxicity of different maintenance strategies in systemic vasculitis <h3>Methods:</h3> A review of published studies of long term outcome in vasculitis and of maintenance therapy in systemic vasculitis <h3>Results:</h3> Once remission has been achieved, relapse is increasingly common, perhaps over 70% in some forms of ANCA associated vasculitis such as GPA. A strategy of induction therapy for one year, without any maintenance results in relapse in most cases of limited GPA. A maintenance regimen is recommended in order to avoid recurrence of the disease, but the evidence base for use of maintenance therapies remains limited. Maintenance is different from treatment of a relapse, usually aiming to prevent recurrence of clinical evidence of disease. We will show the evidence for different types of maintenance regimens and the outcomes in terms of relapse and toxicity with a focus on recently completed clinical trials and observational cohorts in a variety of forms of systemic vasculitis <h3>Conclusion:</h3> The management disease in systemic vasculitis requires induction therapy but increasingly recognised is the importance of a maintenance regimen. Current and future strategies should explore a mechanism based approach, to selectively modify the underlying immunopathogenic mechanisms. <h3>References:</h3> [1] 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. [2] Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, Höglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Stegeman C, Walsh M, Westman K; European Vasculitis Study Group. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011 Mar;70(3):488-94. [3] Jayne D, Blockmans D, Luqmani R, Moiseev S, Ji B, Green Y, Hall L, Roth D, Henderson RB, Merkel PA; Collaborators, Lozano JA, Becker H, Quiroz AC, Carette S, Carrillo-Vazquez S, Cid MC, D"Cruz D, Deodhar A, Flossman O, Garibotto G, Gesualdo L, Hall S, Hauser T, Hellmich B, Kidder D, Kimmel M, Little M, Majdan M, Maksimowicz-McKinnon K, Marder G, Matsievskaia G, Meneses AS, Molloy E, Mueller R, Neuwelt C, Hernandez JR, Specks U, Tesar V, Walsh M. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in ANCA-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol. 2019 Jan 22. <h3>Disclosure of Interests:</h3> Raashid Luqmani Grant/research support from: Roche, Vifor and GSK