B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial.

Objective: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies.

Methods: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104.

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis.

BACKGROUNDBaseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).METHODSA previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299).

Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis.

Background:: Tubulointerstitial inflammation (TII) in lupus nephritis (LN) is associated with a worse prognosis. Vimentin, a filamental antigen, is commonly targeted by activated B-cells in TII. The prognostic importance of high serum anti-vimentin antibodies (AVAs) in LN and their relationship with common lupus autoantibody specificities is unknown.

Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant.

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease.

Outcome of participants with nephrotic syndrome in combined clinical trials of lupus nephritis.

Objective: The outcome of participants with nephrotic syndrome in clinical trials of lupus nephritis has not been studied in detail.

Methods: Collated data from two randomised controlled trials in lupus nephritis, Lupus Nephritis Assessment of Rituximab (LUNAR) and A Study to Evaluate Ocrelizumab in Patients With Nephritis due to Systemic Lupus Erythematosus (BELONG) were analysed. Nephrotic syndrome was defined as albumin <3 g/dL and urine protein/creatinine ratio ≥3.

MRI heterogeneity analysis for prediction of recurrence and disease free survival in anal cancer.

Background: The aim of this study was to evaluate the role of image heterogeneity analysis of standard care magnetic resonance imaging (MRI) in patients with anal squamous cell carcinoma (ASCC) to predict chemoradiotherapy (CRT) outcome. The ability to predict disease recurrence following CRT has the potential to inform personalized radiotherapy approaches currently being explored in novel clinical trials.

Methods: An IRB waiver was obtained for retrospective analysis of standard care MRIs from ASCC patients presenting between 2010 and 2014.

Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE Registry.

Objective: To evaluate the long-term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥ 1 antitumor necrosis factor therapies in the United States (SUNSTONE Registry).

Methods: In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard-of-care follow-up visits at least every 6 months. The primary outcome was the incidence of protocol-defined significant infections.

Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis.

Background And Objectives: Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis.

Design, Setting, Participants, & Measurements: We analyzed 68 participants treated with rituximab.

Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis.

Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes.

Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve.

Effect of Disease Activity, Glucocorticoid Exposure, and Rituximab on Body Composition During Induction Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: We investigated the relationships between glucocorticoid use, disease activity, and changes in body mass index (BMI) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: We analyzed AAV patients enrolled in the Rituximab in AAV trial. Glucocorticoid use, BMI, and disease activity were measured regularly during the trial period.

A population-based study of infection-related hospital mortality in patients with dermatomyositis/polymyositis.

Objective: Dermatomyositis (DM) and polymyositis (PM) are debilitating inflammatory myopathies associated with significant mortality. We evaluated the relative contribution of infection to hospital mortality in a large population-based study of individuals with PM/DM.

Methods: Data derive from the 2007 to 2011 Healthcare Cost and Utilization Project National Inpatient Samples and include all hospital discharges that met a validated administrative definition of PM/DM.

Acute liver failure with thyrotoxicosis treated with liver transplantation.

Objective: We describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF).

Methods: We present a case report and review the relevant literature.

Results: An extensive evaluation excluded possible causes of ALF other than thyrotoxicosis.

Mathematical modeling of cancer radiovirotherapy.

Cancer virotherapy represents a dynamical system that requires mathematical modeling for complete understanding of the outcomes. The combination of virotherapy with radiation (radiovirotherapy) has been recently shown to successfully eliminate tumors when virotherapy alone failed. However, it introduces a new level of complexity.