Ann. Rheum. Dis. 2018 May 03
Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides.
Abstract
Objective
To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides.
Methods
The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed.
Results
Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time.
Conclusion
The rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival.
Trial registration number
NCT00748644.
Related Questions
Are there certain subsets of ANCA vasculitis patients for whom you would consider life long maintenance therapy?
Overall the field is moving towards longer, and sometimes indefinite maintenance therapy. This is because multiple studies have demonstrated that relapse risk increases when maintenance therapy is stopped. I consider indefinite maintenance therapy for the following patients: 1. Frequent relapsers - ...
Do you recommend on-demand versus fixed-schedule dosing for rituximab maintenance in ANCA vasculitis?
This is a fairly hot question in the field, and one that reflects the success we have had with advancing therapy for ANCA-associated vasculitis; it’s nice to have choices! Although there are data for both approaches, there are more data (larger numbers, etc.), in my opinion, for fixed-dosing. The tr...