Background/Purpose: Once ANCA-associated vasculitis (AAV) remission has been achieved with CS and cyclophosphamide (CYC), maintenance therapy usually relies on azathioprine (AZA) or methotrexate. However, 18- and 28-month relapse rates remain high, 15% and 28%, respectively. Although rituximab (RTX) has been demonstrated to be as effective as CYC for induction of complete remission by 6 months, some retrospective studies showed that more than half of the patients without maintenance relapsed within 2 years. The results of a prospective, randomized, controlled trial of RTX vs AZA to maintain AAV remission are reported (MAINRITSAN, NCT 00748644). (Sponsor: Assistance publique Hôpitaux de Paris, Grants: Programme Hospitalier de Recherche Clinique, Rituximab was provided in part by Roche).
Methods: Once remission was obtained with a conventional regimen, patients with newly diagnosed (2/3 of the enrollments) or relapsing (1/3) AAV were randomly assigned to receive a 500-mg RTX infusion on D1, D15, 5.5 months later, then every 6 months for a total of 5 infusions over 18 months, or AZA for 22 months at the initial dose of 2 mg/kg/d. The primary endpoint was the major relapse rate (EULAR/ACR criteria) at 28 months. Other outcome measures were the severe adverse event (SAE) rate (WHO definition) associated with each maintenance regimen. We hypothesized that the RTX arm would have a 50% lower relapse rate than that of AZA, and a similar safety profile.
Results:
Among the 114 patients (50 men/64 women; mean age, 55±13 years; 91 newly diagnosed and 23 relapsers) participating in the study (59 in the AZA arm, 55 in the RTX arm): 86 had granulomatosis with polyangiitis, 23 microscopic polyangiitis and 5 kidney-limited diseases. The main clinical manifestations at diagnosis or last relapse included ENT involvement in 88 (77.2%), lung in 69 (60.5%) and kidney in 82 (71.9%). Eighty-four (73.7%) patients have already completed their 28 months of follow-up; the last patient visit and trial closure are scheduled in 10/2012. So far, major relapses have occurred in 18 (15.7%) patients: 2 (3.6%) in the RTX arm and 16 (27.1%) in the AZA arm, with 3 AZA-arm deaths (1 sepsis, 1 pancreatic cancer, 1 mesenteric ischemia). Thirty-three experienced SAE: 18 related to AZA, 15 to RTX. In the AZA arm, 12 infections (1 fatal) and 1 skin cancer were observed vs 11 infections (none fatal) in the RTX arm.
Conclusion: The results of this study demonstrated that 500 mg of RTX every 6 months was superior to AZA to maintain AAV remission. The infection frequencies were comparable in the 2 arms, and other SAE were infrequent and resolved in most patients.
Disclosure:
L. Guillevin,
None;
C. Pagnoux,
None;
A. Karras,
None;
C. Khoutra,
None;
O. Aumaitre,
None;
P. Cohen,
None;
F. Maurier,
None;
O. Decaux,
None;
H. Desmurs-Clavel,
None;
P. Gobert,
None;
T. Quemeneur,
None;
C. Blanchard-Delaunay,
None;
P. Godmer,
None;
X. Puechal,
Pfizer Inc,
5,
Roche Pharmaceuticals,
5;
P. L. Carron,
None;
P. Y. Hatron,
None;
N. Limal,
None;
M. Hamidou,
None;
M. Ducret,
None;
F. Vende,
None;
E. Pasqualoni,
None;
B. Bonnotte,
None;
P. Ravaud,
None;
L. Mouthon,
None;
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-versus-azathioprine-for-maintenance-in-antineutrophil-cytoplasmic-antibodies-anca-associated-vasculitis/