Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose: Remission of ANCA-associated vasculitides (AAVs) can be induced with combined glucocorticoids and cyclophosphamide or rituximab (RTX) with comparable efficacy.1 RTX superiority to azathioprine was demonstrated for remission maintenance;2 in that trial, at month 28, major relapses occurred in only 5% of the patients on RTX vs 29% taking azathioprine (AZA). Although, at present, neither ANCA-positivity and/or their titers nor peripheral blood CD19 B-cell detection are considered reliable predictors of AAV relapses, relapses are rare when they are negative.3 This trial (MAINRITSAN2, registered with ClinicalTrials.gov, no. NCT01731561) was designed to evaluate RTX use, adapted to ANCA-positivity and/or titer and/or reappearance of circulating CD19 B cells, to maintain AAV remission.
Methods: Patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy with glucocorticoids and cyclophosphamide or rituximab or methotrexate were included in an open-label, multicenter, randomized–controlled trial to compare regimens with RTX given according to ANCA status/titer and/or circulating CD19 B-cell reappearance vs systematic RTX infusions (controls). The experimental arm received fixed, 500-mg RTX infusions on day-0 post-randomization, then every 3 months until month 18, when CD19 lymphocytes exceeded 0/mm3 or ANCA status (reappearance)/titer (higher) differed from the previous determination. Controls received 500 mg of RTX on days 0 and 14 after randomization, and then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom or worsening disease with BVAS>0) at month 28; it was evaluated by an independent Adjudication Committee blinded to treatment arms.
Results: The 162 patients included [117 (72.2%) GPA and 45 (27.8%) MPA] were equally allocated to the experimental arm (n=81; 50%) and control (n=81; 50%) groups. Pre-randomization induction therapy was cyclophosphamide for 100 (61.7%) patients, RTX for 61 (37.7%) or methotrexate for 1 (0.6%). Twenty-one (13%) patients suffered 22 relapses: 14 (17.3%) in 13 experimental arm patients and 8 (9.9%) in 8 controls (P=0.20). Median (interquartile range (IQR)) numbers of RTX infusions were 3 (2–4) for the experimental arm and 5 (IQR 5–5) for controls. Four patients died, 1 of an infectious complication.
Conclusion: AAV relapse rates for patients given individually tailored or systematic RTX-infusion schedules did not differ significantly. However, the experimental arm patients received fewer infusions and lower total RTX doses. 1Stone JH et al. N Engl J Med 2010;363:221–32. 2Guillevin L et al. N Engl J Med 2014;371:1771–80. 3Specks U et al. N Engl J Med 2013;369:417–27.
Disclosure: P. Charles, Hoffmann-La Roche, Inc., 9; B. Terrier, Hoffmann-La Roche, Inc., 9; P. Cohen, Hoffmann-La Roche, Inc., 9; S. Faguer, Hoffmann-La Roche, Inc., 9; A. Huart, Hoffmann-La Roche, Inc., 9; M. Hamidou, Hoffmann-La Roche, Inc., 9; C. Agard, Hoffmann-La Roche, Inc., 9; B. Bonnotte, Hoffmann-La Roche, Inc., 9; M. Samson, Hoffmann-La Roche, Inc., 9; A. Karras, None; N. Jourde-Chiche, Hoffmann-La Roche, Inc., 9; F. Lifermann, Hoffmann-La Roche, Inc., 9; P. Gobert, Hoffmann-La Roche, Inc., 9; C. Hanrotel-Saliou, Hoffmann-La Roche, Inc., 9; P. Godmer, Hoffmann-La Roche, Inc., 9; N. Martin Silva, Hoffmann-La Roche, Inc., 9; G. Pugnet, Hoffmann-La Roche, Inc., 9; M. Matignon, Hoffmann-La Roche, Inc., 9; O. Aumaître, Hoffmann-La Roche, Inc., 9; E. Lazaro, Hoffmann-La Roche, Inc., 9; L. Mouthon, Hoffmann-La Roche, Inc., 9; L. Guillevin, Hoffmann-La Roche, Inc., 9.
To cite this abstract in AMA style:Charles P, Terrier B, Cohen P, Faguer S, Huart A, Hamidou M, Agard C, Bonnotte B, Samson M, Karras A, Jourde-Chiche N, Lifermann F, Gobert P, Hanrotel-Saliou C, Godmer P, Martin Silva N, Pugnet G, Matignon M, Aumaître O, Lazaro E, Mouthon L, Guillevin L. Comparison of Systematic Vs Individually Tailored Rituximab Regimen to Maintain ANCA-Associated–Vasculitis Remission: Results of a Prospective, Randomized–Controlled, Phase 3 Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/comparison-of-systematic-vs-individually-tailored-rituximab-regimen-to-maintain-anca-associated-vasculitis-remission-results-of-a-prospective-randomized-controlled-phase-3-trial/. Accessed June 27, 2017.
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