Individually Tailored vs Fixed-Schedule Rituximab Regimens in ANCA-Associated Vasculitis

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides relapse rates did not differ significantly among patients treated with individually tailored vs fixed-schedule rituximab infusion regimens, according to the results of the phase 3, open-label, multicenter, randomized, controlled Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis-2 (MAINRITSAN2) trial (ClinicalTrials.gov identifier: NCT01731561), published in the Annals of the Rheumatic Diseases.

The investigators sought to compare individually tailored rituximab infusion regimens, based on trimestrial biological parameter monitoring, with fixed-schedule rituximab reinfusion for the maintenance of ANCA-associated vasculitis remission. Patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis whose disease was in complete remission following induction therapy were included in the study.

Patients were randomly assigned to receive maintenance therapy with either an individually tailored (according to laboratory findings, every 3 months) or a fixed-schedule rituximab regimen within 1 month of completion of induction therapy, if they had been treated with cyclophosphamide or methotrexate, or 4 to 6 months after their last rituximab infusion if it had been used to obtain remission.

All patients in the individually tailored group received a rituximab 500-mg infusion at randomization and received rituximab reinfusion only when CD19+ B lymphocytes or ANCA reappeared or when ANCA titer rose markedly based on trimestrial testing for 18 months. Participants on a fixed-schedule rituximab regimen were treated with a rituximab 500-mg infusion on days 0 and 14 postrandomization and then at 6, 12, and 18 months after the first infusion. The researchers defined the primary end point as the number of relapses or worsening disease based on the Birmingham Vasculitis Activity Score >0 at 28 months, determined by an independent adjudication committee blinded to the participants’ treatment group.

A total of 162 patients were included in the analysis, 72.2% of whom had granulomatosis with polyangiitis and 27.8% of whom had microscopic polyangiitis. The mean patient age was 60 years and 42% of the participants were women. Preinclusion induction therapy included 100 patients who received cyclophosphamide, 61 who received rituximab, and 1 who received methotrexate.

At 28 months, 21 patients had experienced 22 relapses: 17.3% (14 of 81) in 13 patients receiving tailored infusion and 9.9% (8 of 81) in 8 of those on the fixed schedule (P =.22). Participants in the tailored-infusion vs fixed-schedule groups received 248 vs 381 infusions, respectively, with a median of 3 vs 5 administrations.

The investigators concluded that although ANCA-associated vasculitides relapse rates did not differ significantly between participants treated with individually tailored vs fixed-schedule rituximab regimens, patients in the individually tailored group received fewer rituximab infusions and lower total rituximab doses. The authors noted that this was in part because of the personalized patient care received by these patients.

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Reference

Charles P, Terrier B, Perrodeau É, et al; French Vasculitis Study Group. 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) [published online April 25, 2018].  Ann Rheum Dis. doi: 10.1136/annrheumdis-2017-212878