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.
Contributors PCh and LG conceived and planned the study. ÉP and PR designed and carried out the statistical analyses. PCh wrote the first draft of the manuscript and all authors contributed to subsequent revisions. All other authors entered data, participated in devising the protocol and reviewed all versions of the manuscript.
Funding This study was funded by a research grant from the French Ministry of Health (PHRC National 2011 AOM11145) and sponsored by the Assistance Publique–Hôpitaux de Paris. Hoffmann-La Roche provided rituximab for the study.
Competing interests BT has received consulting and speaking fees (Roche, LFB, Grifols, GSK). MH has received personal fees from Roche. AK has received personal fees and non-financial support from Roche. XP has received speaking fees and honoraria (Pfizer, LFB, Roche) and a research grant (Pfizer).
Ethics approval The Ethics Committee (Comité de Protection des Personnes Île-de-France 1 (Paris)) approved the study.
Collaborators Other investigators and members of the French Vasculitis Study Group who participated in the study are listed in the online supplementary.