Ann. Rheum. Dis. 2018 Apr 25
Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).
Abstract
Objective
To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs).
Methods
Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group.
Results
Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations.
Conclusion
AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions.
Trial registration number
NCT01731561; Results.
Related Questions
How do you approach using CD 19/20 levels to redose Rituximab for ANCA associated vasculitis?
In the MAINRITSAN 2 trial, a tailored rituximab regimen adapted to ANCA-positivity or ANCA-titre change and/or circulating CD19+ B cell repopulation was compared with fixed-schedule rituximab infusions.There was no significant difference in relapse rates between the fixed-dose and tailored-dose arms...
Is there a role for monitoring serum ANCAs to assess ANCA associated vasculitis disease activity?
This is (and remains) a somewhat controversial question. ANCA titers do appear to rise in anticipation of disease flares and patients with persistent titers appear to have more flares. This is especially true for PR3 ANCAs. However, the proximity of flares to rising ANCA titers is not terribly close...
What clinical factors do you use to determine timing of on-demand dosing of rituximab in ANCA vasculitis maintenance therapy?
I tend to use scheduled dosing (q 6 months) with RTX for maintenance in my GPA/MPA patients, but will occasionally use "on-demand" dosing in those who are eager to minimize their RTX, do not tolerate the infusions well, or occasionally those who have lower risks of flare (mild disease, no history of...
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...