Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial.

BACKGROUND: Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). OBJECTIVE: To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT02433522). SETTING: 39 clinical centers in France. PATIENTS: 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy. INTERVENTION: Rituximab or placebo infusion every 6 months for 18 months (4 infusions). MEASUREMENTS: The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0. RESULTS: From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (P = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group. LIMITATION: Potential selection bias based on previous rituximab response and tolerance. CONCLUSION: Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy. PRIMARY FUNDING SOURCE: French Ministry of Health and Hoffmann-La Roche.

No evident association of nasal carriage of Staphylococcus aureus or its small-colony variants with cotrimoxazole use or ANCA-associated vasculitis relapses.

OBJECTIVE: To identify the role of Staphylococcus aureus (SA) or its intracellular small-colony variant phenotype (SCV) with co-trimoxazole (CTX) or ANCA-associated vasculitis (AAV) activity. METHODS: All consecutive AAV patients with granulomatosis with polyangiitis (GPA), eosinophilic GPA or microscopic polyangiitis, followed at the French National Vasculitis Referral Center (09/2012-05/2013), and hospitalized non-AAV controls, exclusively for SA/SCV carriage comparisons, were enrolled. All had bilateral anterior nasal swab cultures. Nasal SA or SCV carriage was determined and associations with relapse(s), BVAS, ANCA-positivity, anti-staphylococcal and immunosuppressant use, were analysed ⩾4 years post-inclusion. RESULTS: Nasal SA carriage rates did not differ among AAVs (P = 0.53): GPA (24/80; 30%), EGPA (7/28; 25%) and microscopic polyangiitis (3/11; 27.3%); and the rate was less frequent in controls than in GPA patients not taking CTX (P = 0.04). AAV patients taking CTX prophylaxis had less nasal SA carriage (8.7% vs 36.2%; P = 0.02). Nasal SA carriage or CTX use did not modify relapse rates, BVAS or ANCA-positivity at inclusion or during follow-up. Nasal SCV carriage, found in 15/207 (7.2%) patients, was similar for GPA (10/24; 41.7%), microscopic polyangiitis (2/7; 28.6%) and eosinophilic GPA (2/3; 66.7%), but higher (P = 0.02) than controls (1/14; 7.1%). SCV carriage by AAV groups did not modify relapse rates or ANCA positivity at inclusion or during follow-up; a trend towards higher BVAS was observed only for anti-PR3 ANCA patients. CONCLUSION: Nasal SA or SCV carriage was comparable among AAVs but more frequent than in controls. Nasal SA or SCV carriage and CTX use did not modify AAV relapse rates.