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Objective. From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA.Methods. Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg). Results. Compared to controls, levels of Th17 cells (CD4؉IL-17؉

ObjectiveTo 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).MethodsPatients 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.ResultsAmong 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.ConclusionAAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions.Trial registration numberNCT01731561; Results.

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ObjectivesTo assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients.MethodsNationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model.ResultsAmong 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients.ConclusionRTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

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Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was in-

Stroke, especially in the vertebrobasilar territory, is more likely to occur in patients with GCA who experience recent ophthalmic ischemic symptoms and who exhibit low inflammatory variables.