ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 16L

Comparison of Systematic Vs Individually Tailored Rituximab Regimen to Maintain ANCA-Associated–Vasculitis Remission: Results of a Prospective, Randomized–Controlled, Phase 3 Trial

Pierre Charles1, Benjamin Terrier2, Pascal Cohen3, Stanislas Faguer4, Antoine Huart5, Mohamed Hamidou6, Christian Agard7, Bernard Bonnotte8, Maxime Samson8, Alexandre Karras9, Noémie Jourde-Chiche10, François Lifermann11, Pierre Gobert12, Catherine Hanrotel-Saliou13, Pascal Godmer14, Nicolas Martin Silva15, Grégory Pugnet16, Marie Matignon17, Olivier Aumaître18, Estibaliz Lazaro19, Luc Mouthon20, Loïc Guillevin21 and French Vasculitis Study Group, 1Service de Médecine Interne, Hôpital Cochin, Paris, France, 2Internal Medicine, Cochin University Hospital, Paris, France, 3Department of Internal Medicine, Referral Center for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, Paris, France, 42Service de Néphrologie et Immunologie Clinique, Centre Hospitalier Universitaire (CHU) de Toulouse, Toulouse, France, 5CHU, Toulouse, France, 6Internal Medicine Department, Internal Medicine Department, Nantes University Hospital, Nantes, France, 7Internal Medicine Department, Nantes University Hospital, Nantes, France, 8Department of Internal Medicine and Clinical Immunology, Hôpital François Mitterrand, CHU de Dijon, Dijon, France, 9Nephrology, HEGP, Paris, France, 10Vascular Research Center of Marseille, Aix-Marseille Univ., Vascular Research Center of Marseille, Marseille, France, 11CH Dax, Dax, France, 12Nephrology, Centre Hospitalier d'Avignon, Avignon, France, 13CHU Cavale Blanche, Brest, Brest, France, 14CH Vannes, Vannes, France, 15Department of Internal Medicine, Caen University Hospital, Caen, France, 16Service de Médecine Interne, CHU de Toulouse, Toulouse, Toulouse, France, 17Service de Néphrologie, Hôpital Henri-Mondor, Créteil, Créteil, France, 18CHU Pitié-Salpêtrière - Department of Internal Medicine 2. Referal center for SLE/APS, Paris, France, 19Service de Médecine Interne et Maladies Infectieuses, CHU de Bordeaux, Pessac, France, 20Internal Medicine, Referral Center for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, Paris, France, 21National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: October 19, 2016

Keywords: , ,

Session Information

Date: Tuesday, November 15, 2016

Title: ACR Late-Breaking Poster Session

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). https://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 .

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