Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Rituximab Maintenance Therapy for Relapsed Wegener's Granulomatosis and Microscopic Polyangiitis.

Roubaud-Baudron3,  Claire, Pagnoux3,  Christian, Le Guen3,  Julien, de Menthon3,  Mathilde, Camps1,  Sandra, Aouizerate3,  Jessie, Le Guern3,  Véronique

Department of Pharmacy, Hopital COchin, APHP, Universite Paris Descartes
Hopital Cochin-Paris Univ, Paris, France
Internal Medicine, Hopital Cochin, APHP, Universite Paris Descartes, France

Background:

After induction therapy, 50% of Wegener's granulomatosis (WG) and 33% of microscopic polyangiitis (MPA) patients relapse. Rituximab (RTX) effectively induced remission of 1st relapses and refractory disease, but its place in remission maintenance is unknown. In this study, we retrospectively analyzed RTX efficacy as maintenance therapy.

Methods:

Patients entered in our department database who had received >=2 RTX maintenance infusions, regardless of induction regimen, between 2003 and 2010, were selected. Their main characteristics (diagnosis, clinical and biological data (ANCA, CD19 and Ig levels) and treatment histories), RTX maintenance details (number, dose and periodicity), tolerance and outcomes were analyzed.

Results:

Four MPA and 24 WG patients (median age 55.5 (range 18–78) yr; 18 (58%) men) were included. The cumulative median cyclophosphamide (CYC) dose was 48 (range 10–250) g. At last relapse, patients had several organ involvements: 19 ENT, 17 lung, 11 arthralgias, 11 fever, 9 nephropathy, 3 neuropathy and/or 4 eyes.

Induction treatment had been RTX for 21, conventional corticosteroid (CS)+CYC for 5, and IVIg for 2 (1 also with methotrexate). RTX maintenance (375 mg/m2 biannually for 15 patients, 1 g biannually for 4, 1 g yearly for 3 and different regimens for 6) was chosen because RTX had obtained remission for 21, cytotoxic agent side effects for 2, persistent manifestations after >4 yr of azathioprine (AZA) or mycophenolate mofetil (MMF) for 1 each, previous relapse(s) under cytotoxic maintenance therapy for 2, or renal failure for 1. Patients had received 4 (range 2–10) RTX infusions at 38 (range: 21–97) months of follow-up since their last relapses. Cotreatments included CS for 23 (82%) patients and other cytotoxic agents (AZA for 5, MMF for 5, leflunomide for 1 and/or MTX for 4) for 14 (50%). At the last assessment, 5 (17%) patients were still taking cytotoxic agent(s); median CS dose was 5 (range: 2–20) mg/day. RTX infusions were well-tolerated; 3 patients developed infections (1 cutaneous abscess, 1 otitis and 1 H1N1-flu death).

Two major pulmonary relapses (at follow-up months 48 & 6) and 2 minor ENT relapses (at follow-up months 108 & 34) occurred. Fifteen patients had hypogammaglobulinemia (predominantly IgM). Notably, the 3 patients not CD19-depleted did not relapse. Nine (including 3/4 who relapsed) patients' CD19 levels rose before their biannual RTX infusion. Five patients ANCA-negative at vasculitis onset, remained so. ANCA levels increased before reinfusion in 7 (including 3/4 who relapsed) patients. Overall, at their last assessment, mean ANCA titers for all 28 patients had declined significantly since the last relapse and the last RTX infusion (ANOVA, p<0.0001).

Conclusions:

RTX effectively maintained remission and was well-tolerated. It can be indicated, especially for noncompliant patients or when cytotoxic drugs are contraindicated. Only 2 major relapsed occurred. It is too early to conclude as to the place of CD19 and ANCA levels as indicators to determine infusion periodicity. The ongoing randomized controlled "MAINRITSAN" trial was designed to compare RTX to AZA maintenance therapy for ANCA-associated vasculitides.

To cite this abstract, please use the following information:
Roubaud-Baudron, Claire, Pagnoux, Christian, Le Guen, Julien, de Menthon, Mathilde, Camps, Sandra, Aouizerate, Jessie, et al; Rituximab Maintenance Therapy for Relapsed Wegener's Granulomatosis and Microscopic Polyangiitis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2041
DOI: 10.1002/art.29806

Abstract Supplement

Meeting Menu

2010 ACR/ARHP