Maintenance of Remission in ANCA-Associated Vasculitis

Third, different induction regimens have been found to be associated with different relapse rates in the setting of randomized trials in which induction regimens differed but maintenance regimens were the same in all groups. This finding has been made even in the setting in which the initial effectiveness of the induction regimens appeared to be the same. Thus, initial use of methotrexate or intravenous cyclophosphamide has been associated with higher relapse rates than oral cyclophosphamide.^1,3

A recent trial showing that rituximab was equivalent to oral cyclophosphamide for remission-induction (RAVE) may be more difficult to interpret with regard to relapse rates, since the cyclophosphamide group received azathioprine to complete 18 months of standard treatment, whereas the rituximab group did not receive any additional treatment, and it is presumed that the drug’s effect (based on return of circulating B cells) had worn off in nearly all patients by Month 18.⁴ The key 18-month clinical outcome of RAVE is not yet published but was presented at the 2011 ACR annual meeting: Relapse rates were the same in patients who received one course of rituximab and in patients who continued to receive azathioprine after cyclophosphamide.⁵ Thus, as of Month 18, either induction therapy with rituximab led to lower subsequent relapse rates than induction with oral cyclophosphamide, or maintenance therapy with azathioprine had little or no benefit.

The RAVE trial design therefore serves as a reminder that it is worth considering the evidence that maintenance treatment is effective at all. The data addressing this question are limited and mostly observational but, I think, still convincing. First, early in the era of successful treatment of GPA with cyclophosphamide, it was noted that patients treated for only a few months were very likely to relapse, which led to the recommendation to continue cyclophosphamide for a year after achievement of remission.⁶ Second, addition of sulfamethoxizole-trimethoprim to a variety of other medications during remission was associated with reduced relapse rates in a randomized trial.⁷ Third, comparison of two groups of patients separated in time but otherwise managed very similarly at one center indicated that relapse rates were much lower in patients given methotrexate rather than sulfamethoxizole-trimethoprim after remission induction.⁸