; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin.

More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).

These results do not support the primary hypothesis that methotrexate is safer than azathioprine. The two agents appear to be similar alternatives for maintenance therapy in patients with Wegener's granulomatosis and microscopic polyangiitis after initial remission. (ClinicalTrials.gov number, NCT00349674.)

IntroductionImmune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts and may be responsible for mucocutaneous bleeding of variable severity. 1 ITP is usually chronic (Ͼ 6 months) in adults and, after this time, the probability of spontaneous remission is low. Standard management is to initiate steroids, anti-Rh 0 (D) immune globulins, and/or intravenous immunoglobulins (IVIgs) for the more severe forms. [2][3][4][5] The response rate is high but most often transient. That the spleen plays a major role in the removal of damaged platelets has long been known and, to date, splenectomy is still considered the "gold standard" treatment in many countries for the management of chronic ITP with platelet counts less than 30 ϫ 10 9 /L, especially when hemorrhagic complications are present. Approximately two thirds of chronic ITP patients who undergo splenectomy achieve lasting responses. 6 As suggested in the guidelines of the American Society of Hematology (ASH) 7 and the British Committee for Standards in Hematology (BCSH), 8 splenectomy should be considered the main second-line therapy for patients who fail to respond durably to first-line therapy, with persistent platelet counts less than 30 ϫ 10 9 /L. However, increasing numbers of patients are reluctant to undergo splenectomy and physicians are hesitant to recommend it. 9,10 In addition, the risk of overwhelming postsplenectomy infections, although rare, is not predictable and represents a major concern. 11-13 Moreover, some authors reported that, despite initial good responses to splenectomy, the risk of late relapse persists during long-term follow-up 14,15 and severe morbidity resulting from surgery is associated with 11% to 30% postoperative complications requiring prolonged hospitalization or readmission. 11,16 For these reasons, an effective and safe alternative to splenectomy would improve management of chronic ITP.Rituximab is a chimeric, humanized monoclonal antibody directed against the CD20 determinant on B cells. It was initially developed for the treatment of malignant lymphoma but has also been used in autoantibody-mediated disorders, such as rheumatoid arthritis, 17 systemic lupus erythematosus, 18 autoimmune hemolytic anemia, 19 or thrombotic thrombocytopenic purpura. 20 Case reports and several uncontrolled studies described its promising results in ITP patients. Arnold et al 21 conducted a systematic review of published reports on rituximab use in adults with chronic ITP. A complete response, usually observed 3 to 8 weeks after the first infusion, was obtained in 46% of patients. The median response duration was 10.5 months (interquartile range [IQR]: 6.3-17.8 months), but long-term For personal use only. on May 10, 2018. by guest www.bloodjournal.org From responses were not mentioned in all published studies. Arnold et al 21 pointed out the heterogeneity of patients' prior rituximab use and particularly their splenectomy status. Moreover, the short follow-up in some reports and the possible bias due to th...