Long-Term Follow-Up of Patients with Scleritis After Rituximab Treatment Including B Cell Monitoring

Purpose: We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses. Methods: We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment. Results:Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3–13), and all reached remission. The median follow-up was 101 months (range 9–138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions.Conclusions: RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis.</p

Are Patients at Risk for Recurrent Disease Activity After Switching From Remicade® to Remsima®? An Observational Study

Background: Since the late ‘90s, infliximab (Remicade®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade® (originator infliximab) and its biosimilar Remsima® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade® to Remsima® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade® were switched to Remsima® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima® treatment, one withdrew from the study and one received additional corticosteroid therapy. Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade® to Remsima®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade® to Remsima®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening

Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory drugs, but side effects include retinopathy and vision loss. The objective of this study was to examine the effect of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro. Permeability of ARPE-19 cell monolayers was determined using Fluorescein isothiocyanate (FITC)-labeled dextran. The influence of CQ and HCQ on cell death and the expression tight junction molecules was examined. CQ and HCQ significantly increased ARPE-19 monolayer permeability after 3 and 18 h, respectively, and enhanced mRNA levels for claudin-1 and occludin. Cytotoxicity was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE barrier permeability in vitro, independent of cytotoxicity or loss of zonula occludens-1, claudin-1, and occludin expression. Our findings suggest that CQ/HCQ-induced permeability of the RPE layer may contribute to blood-retinal barrier breakdown in case of CQ/HCQ-induced retinopathy

Retinal pigment epithelial cells display specific transcriptional responses upon TNF-α stimulation

BACKGROUND/AIMS: Tumour necrosis factor-α (TNF-α) is a key mediator of ocular inflammation and its interaction with the retinal pigment epithelium (RPE) may be a driving force in vitreoretinal disorders such as age-related macular degeneration, proliferative vitreoretinopathy (PVR) and diabetic retinopathy. Under inflammatory conditions, the ability of RPE cells to maintain the blood-retinal barrier and immune privilege may be lost and proliferation of RPE cells is facilitated. To gain insight into the effects of TNF-α on RPE cells, a gene expression study was performed. METHODS: ARPE-19 and HT-29 cells were stimulated with 50 ng/mL TNF-α for 6 h. Gene expression patterns were compared between stimulated and control cells using whole genome gene expression arrays. Data were analysed using Partek and OmniViz and validated using quantitative RT-PCR. Functional annotation analysis was performed using Ingenuity and DAVID. RESULTS: A total of 97 genes were uniquely modulated by TNF-α in ARPE-19 cells compared with HT-29 cells (86 upregulated and 11 downregulated). Most commonly affected biological processes were apoptosis, cell motility and cell signalling. The highest upregulated gene was EFNA1. Among the downregulated genes were transcription factors implicated in ocular development (SIX3, PAX6) and modulation of p53-mediated apoptosis (CITED2). CONCLUSIONS: This study provides insight into the unique responses of RPE cells to TNF-α stimulation and suggests a role for genes involved in apoptosis and retinal epithelial development. These findings contribute to our understanding of the behaviour of RPE cells under inflammatory conditions and the crucial role of RPE cells in vitreoretinal diseases