Background/Purpose
Rituximab (RTX) was shown to be as effective as cyclophosphamide to induce remission in patients with ANCA-associated vasculitis (AAV). The prospective MAINRITSAN trial compared RTX to azathioprine (AZA) to maintain AAV remission after a corticosteroid-and-cyclophosphamide induction regimen. Patients were randomly assigned to receive 500-mg RTX infusions on D1, D15 and 5.5 months later, then every 6 months until 18 months, or AZA for 22 months (initial dose: 2 mg/kg/d). Trial results demonstrated that RTX was superior to AZA at maintaining AAV remission during the planned 28 months of observation. Extended follow-up showed that late relapses could occur in RTX-treated patients. In this follow-up study, we analyzed these relapses occurring after RTX-maintenance therapy, aiming to identify factors predictive of them.
Methods
For the 57 patients randomized to the RTX arm, data on their relapses were recorded during the 28-month trial and extended follow-up, and factors predictive of relapse were identified with univariate and multivariate analyses.
Results
Fifty-six patients (men 64%; mean age 54±13 years) were analyzed, with median follow-up at 50 months. Fifteen (26%) patients experienced at least 1 major relapse after a median of 40 (range 8–52) months. Three relapses occurred during the 28-month trial, while 12 relapses occurred during extended follow-up. According to univariate analysis, relapse-associated factors were: granulomatosis and polyangiitis (Wegener’s) diagnosis [HR 5.39 (0.70–41.5), P=0.11], proteinase-3 (PR3)-ANCA at AAV diagnosis [HR 6.29 (0.82–48.2), P=0.08], glomerular filtration rate <60 mL/min [HR 0.43 (0.14–1.36), P=0.15], and persistent ANCA-positivity 6 months [HR 2.21 (0.80–6.12), P=0.13] and 12 months [HR 4.45 (1.60–12.4), P<0.01] after starting maintenance therapy. Multivariate analysis retained the following factors as being significantly associated with relapse: PR3-ANCA–positivity [HR 12.5 (1.47–106), P=0.02] and persistent ANCA-positivity at 12 months [HR 7.79 (2.51–24.2), P<0.01]. The 50-month cumulative relapse rates were 82.5, 23.4 and 0%, respectively, for patients with PR3-ANCA and ANCA positivity at 12 months, patients with PR3-ANCA and negative ANCA at 12 months, and those with myeloperoxidase-ANCA.
Conclusion
A quarter of AAV patients who received RTX-maintenance therapy experienced late relapses during extended follow-up. Factors predictive of relapse for these patients were PR3-ANCA–positivity and persistent ANCA positivity 12 months after starting maintenance therapy. Our findings suggest that pursuing RTX-maintenance therapy in these patients could be beneficial to prevent relapses.
Disclosure:
B. Terrier,
None;
C. Pagnoux,
None;
G. Geri,
None;
A. Karras,
None;
C. Khouatra,
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. Puéchal,
None;
L. Mouthon,
None;
L. Guillevin for the French Vasculitis Study Group,
None.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-predictive-of-anca-associated-vasculitis-relapse-in-patients-given-rituximab-maintenance-therapy/