Reducing the Number of Rituximab Infusions at Onset of Maintenance Therapy for ANCA-associated Vasculitides: Results of a Post Hoc Analysis from a Randomized–controlled Trial

Pierre Charles¹, Agnes Dechartres ², Benjamin Terrier ³, Pascal Cohen ³, Stanislas Faguer ⁴, Antoine Huart ⁴, Mohamed Hamidou ⁵, Christian Agard ⁵, Bernard Bonnotte ⁶, Maxime Samson ⁷, Alexandre Karras ⁸, Noémie Jourde-Chiche ⁹, François Lifermann ¹⁰, Pierre Gobert ¹¹, Catherine Hanrotel-Saliou ¹², Pascal Godmer ¹³, Nicolas Martin-Silva ¹⁴, Grégory Pugnet ¹⁵, Marie Matignon ¹⁶, Olivier Aumaitre ¹⁷, Jean-François Viallard ¹⁸, François Maurier ¹⁹, Nadine Meaux Ruault ²⁰, Sophie Rivière ²¹, Jean Sibilia ²², Xavier Puéchal for the French Vasculitis Study Group ³, Luc Mouthon ³ and Loic Guillevin ³, ¹Institut Mutualiste Montsouris, Paris, France, ²APHP, Paris, France, ³National Referral Center for Rare Systemic Autoimmune Diseases Paris Cochin, Paris, France, ⁴CHU Toulouse, Toulouse, France, ⁵CHU Nantes, Nantes, France, ⁶Service de Médecine Interne et Immunologie Clinique, CHU Dijon Bourgogne, Hôpital François Mitterrand, Dijon ; Université Bourgogne-Franche Comté, INSERM, EFS BFC, UMR1098, F-21000 Dijon, Dijon, France, ⁷CHU Dijon, Dijon, France, ⁸Paris HEGP, Paris, France, ⁹APHM, Marseille, Marseille, France, ¹⁰CH Dax, Dax, France, ¹¹CH Avignon, Avignon, France, ¹²CHU Brest, Brest, France, ¹³CH Bretagne-Atlantique, Vannes, France, ¹⁴CHU Caen, Caen, France, ¹⁵CHU de Toulouse, Hôpital Purpan, Service de Médecine Interne, Toulouse, France, ¹⁶APHP, Créteil, France, ¹⁷CHU Clermont Ferrand, Clermont Ferrand, France, ¹⁸CHU Bordeaux, Bordeaux, France, ¹⁹Service de Médecine Interne, Hôpital Belle Isle, Metz, Metz, France, ²⁰CHU Besançon, Besançon, France, ²¹CHU Montpellier, Montpellier, France, ²²CHU Strasbourg, Strasbourg, France

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, Vasculitis, Wegener's granulomatosis and polyangiitis

Session Information

Date: Monday, November 11, 2019

Title: Vasculitis – ANCA-Associated Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Rituximab (RTX) superiority over azathioprine to maintain ANCA-associated vasculitis (AAV) remission was demonstrated.The MAINRITSAN2 trial was designed to compare an individually tailored RTX-infusion schedule to 5 RTX infusions at a predefined schedule. The tailored-regimen group received a 500-mg RTX infusion at randomization (day (D) 0), with reinfusion only when CD19 lymphocytes or ANCA had reappeared, or ANCA titer rose markedly, based on testing every 3 months until month (M) 18. The fixed-schedule group received RTX (500 mg) on D0 and D14, then at M6, M12 and M18. AAV relapse rates did not differ significantly between the 2 groups at M28. The objective of this post hoc analysis was to evaluate the effect of omitting the D14 500-mg RTX infusion on early AAV-relapse rates.

Methods: MAINRITSAN2-trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free survival rates in each arm as primary endpoints. Relapses were defined as reappearance or worsening of AAV symptoms, i.e., BVAS >0. Exploratory sub-group analyses were run according to cyclophosphamide or rituximab induction and newly-diagnosed or relapsing AAV.
Other endpoints were ANCA status and titer, and CD19+ B-cell–count evolutions.

Results: At M3, M6, M9 and M12, respectively, among the 161 patients included, 79/80 (98.8%), 76/80 (95%), 74/80 (92.5%) and 73/80 (91.3%) from D0, and 80/81 (98.8%), 78/81 (96.3%), 76/81 (93.8%) and 76/81 (93.8%) from D0+D14 groups were alive and relapse-free. No between-group differences were observed. Results were not affected by cyclophosphamide or rituximab induction, or newly-diagnosed or relapsing AAV. On D0, a higher percentage of D0-infusion patients were ANCA-positive and that difference remained stable at M12. Median (IQR) circulating CD19+ B-cell counts/mm³ on D0, and at M3, M6, M9 and M12, respectively, were: 14 (1–44), 0 (0–0), 0 (0–1), 0 (0-4) and 0 (0–2) for the D0-infusion group; and 9 (0–35), 0 (0–0), 0 (0–2), 0 (0–1) and 0 (0–2) for the D0+D14-infusion group. Those results remained unchanged in the sub-group analyses

Conclusion: Eliminating the D14 rituximab remission-maintenance dose did not seem to impact the relapse-free survival rate at M12.

Disclosure: P. Charles, None; A. Dechartres, None; B. Terrier, Grifols, 8, GSK, 8, LFB, 8, Roche, 8; P. Cohen, None; S. Faguer, None; A. Huart, None; M. Hamidou, Roche, 8; C. Agard, None; B. Bonnotte, None; M. Samson, None; A. Karras, Roche, 8; N. Jourde-Chiche, None; F. Lifermann, None; P. Gobert, None; C. Hanrotel-Saliou, None; P. Godmer, None; N. Martin-Silva, None; G. Pugnet, None; M. Matignon, None; O. Aumaitre, None; J. Viallard, None; F. Maurier, None; N. Meaux Ruault, None; S. Rivière, None; J. Sibilia, None; X. Puéchal for the French Vasculitis Study Group, LFB, 8, Pfizer, 2, 8, Roche, 8; L. Mouthon, None; L. Guillevin, None.

To cite this abstract in AMA style:

Charles P, Dechartres A, 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, Aumaitre O, Viallard J, Maurier F, Meaux Ruault N, Rivière S, Sibilia J, Puéchal for the French Vasculitis Study Group X, Mouthon L, Guillevin L. Reducing the Number of Rituximab Infusions at Onset of Maintenance Therapy for ANCA-associated Vasculitides: Results of a Post Hoc Analysis from a Randomized–controlled Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/reducing-the-number-of-rituximab-infusions-at-onset-of-maintenance-therapy-for-anca-associated-vasculitides-results-of-a-post-hoc-analysis-from-a-randomized-controlled-trial/. Accessed .

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