RESUMO
OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Azatioprina , Humanos , Azatioprina/uso terapêutico , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Recidiva , Indução de Remissão , Resultado do Tratamento , Ciclofosfamida/uso terapêutico , Anticorpos Anticitoplasma de NeutrófilosRESUMO
Clinically apparent venous thromboembolism (VTE) occurs in approximately 7% of patients with membranous nephropathy. Hypoalbuminemia at diagnosis is an independent risk factor for VTE, and risk increases significantly as albumin falls. Optimal prophylactic and treatment anticoagulation regimens in the nephrotic syndrome remain unproven but novel oral anti-coagulants have become attractive therapeutic options. We describe a patient diagnosed with anti-phospholipase A2 receptor antibody positive membranous nephropathy and recurrent VTE while on therapeutic dosing of apixaban. A direct factor Xa inhibitor, apixaban has been shown to be non-inferior to warfarin for the treatment of VTE in the general population. However, because it is highly protein-bound, apixaban may have altered pharmacokinetics and pharmacodynamics in patients with nephrotic syndrome and hypoalbuminemia. This case report highlights the need for further studies of direct oral anticoagulants to fully assess their effectiveness in this high-risk population.