Lupus nephritis - case report of an uncommon succession of therapies

Background. Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE) and often occurs within the first five years after diagnosis. Case report. A 33-year-old woman with SLE (arthritis; cutaneous involvement; Raynaud phenomena, vasculitis, pleural effusion, hematological and immunological abnormalities), under treatment with glucocorticoids and hydroxychloroquine developed focal proliferative LN, which progressed under treatment with belimumab. Consequently, intravenous cyclophosphamide and low-dose rituximab were used to induce LN remission, while maintenance therapy relied on mycophenolate mofetil. Conclusions. The case illustrates an uncommon succession of therapies for SLE and LN, with belimumab preceding cyclophosphamide. The decision to induce remission with cyclophosphamide was based on histological aspects of the renal biopsy. Although current recommendations permit the association of belimumab and cyclophosphamide, there is very little practical experience to support it

Systemic lupus erythematosus – the discrepancy between renal impairment and clinical and immunological manifestations

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement, most commonly targeting the skin, joints and kidneys. The existence and type of renal involvement influence the prognosis and this information may be crucial when it comes to establishing the optimal therapy. We present the case of a patient with SLE with skin involvement (vasculitis), joint manifestations and immunological markers remitted under synthetic remissive treatment but with severe renal damage diagnosed at the renal biopsy as a glomerulosclerosis type focal segmental podocytopathy (FSGS) collapsing variant associated with a possible ultrastructural defect of the glomerular basement membrane in the context of the disease with a severe prognosis

Radiation-Induced Dose and Single Event Effects in Digital CMOS Image Sensors

This paper focuses on radiation-induced dose and single event effects in digital CMOS image sensors using pinned photodiodes. Proton irradiations were used to study cumulative effects. As previously observed, the dark current is the main electrical parameter affected by protons. The mean dark current increase appears proportional to Srour's universal damage factor. Therefore, the degradation is mainly attributed to displacement damage in the pinned photodiode. Heavy ion tests are also reported in this work. This study focuses on single event effects in digital CMOS imagers using numerous electronic functions such as column ADCs, a state machine and registers. Single event transients, upsets and latchups are observed and analyzed. The cross sections of these single events are transposed to specific space imaging missions in order to show that the digital functions can fit the mission requirements despite these perturbations

A report on the adverse events of special interest from the Romanian Registry of Rheumatic Diseases in patients treated with biologic and targeted synthetic disease-modifying anti-rheumatic drugs during 2022

Background. The evolution of the therapeutic arsenal in inflammatory rheumatic diseases has dramatically improved their evolution and prognosis. On the other hand, the information of the safety data, especially for conditions that may appear in a longer time of exposure, are not reflected by clinical trials, due to their limited time design. Patient registries are a valuable source of safety data applicable to real-world (unselected) patients. The evaluation of these data completes the evidence from the various development programs, with the aim of more concrete knowledge of each therapeutic class (therapeutic agent). Aim. The present report descriptively presents the adverse events (AE) of special interest, recorded by the Romanian Registry of Rheumatic Diseases (RRBR), during 2022, in relation to the dynamics of the recent years. Methods. The observational study included all AEs reported in the RRBR in 2022, their severity class, the relationship with exposure to the therapeutic agent. Results. For a cohort of 10676 patients who were exposed to at least one course of treatment, with data in the RRBR during 2022, there were 669 AEs reported: 432 reports for patients with rheumatoid arthritis (RA), 195 records for patients with ankylosing spondylitis (AS) and 42 reports for patients with psoriatic arthritis (PsA). The most common AEs were infections, especially in RA patients. Of all AEs, 94 (14%) were serious AEs, the majority reported in the RA group (16%). A number of 15 MACE, 13 solid malignancy and 19 deaths were reported in the last year. Conclusion. The distribution of EA by disease, the dominance in RA, as well as the distribution by therapeutic groups is in accordance with scientific data, with the exception of breast cancer, which is more frequently reported in RRBR. EA are underreported in the destinated section in the RRBR, an aspect that gives a limit of this report. This represents an unmet need in terms of safety data reporting, that calls for increased knowledge of EA reporting requirements

Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naive patients with rheumatoid arthritis

Objectives To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). Methods Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan–Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. Results 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. Conclusion In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.Peer reviewe

Treatment of axial spondyloarthritis patients with biologic disease-modifying anti-rheumatic drugs in 2022 - data from the Romanian Registry of Rheumatic Diseases

Objective. The objective of this cross-sectional study was to analyze data available in the Romanian Registry of Rheumatic Diseases (RRBR) in 2022 for axial spondyloarthritis (axSpA) patients treated with biologic disease modifying anti-rheumatic drugs (bDMARDs). Methods. From the RRBR electronic database were collected multiple variables, including patient’s demographic and clinical characteristics, treatment characteristics, patterns of treatment use (initiations, continuations, switching, tapering), and treatment efficacy data of axSpA patients, from 1 January 2022 to 31 December 2022. Results. In 2022, a total of 4315 axSpA patients were registered in the RRBR database: 70% were men, 48.4 years mean age, 13.3 years mean disease duration, 90% with radiographic axSpA, with high prevalence of extra-musculoskeletal manifestations and cardiovascular comorbidities. Most patients (88%) were treated with a tumor necrosis factor inhibitor (TNFi), usually in monotherapy. The most frequently prescribed bDMARDs were adalimumab (36%), etanercept (32%) and secukinumab (12%). The uptake of biosimilars reached one third of patients from molecules with available biosimilars in 2022. Most patients had a good clinical response, irrespective of clinical form, disease duration, type of medication or line of treatment. Medication switching was needed in 10% of patients, the main reason for switching was secondary loss of efficacy. Medication tapering was implemented in 11% of patients, and it was successful in 90% of cases. Conclusion. Data from RRBR provide a valuable real-world view of clinical practice at the national level regarding biologic treatment of axSpA patients

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations

EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis

Copyright © 2017 BMJ Publishing Group Ltd & European League Against Rheumatism. All rights reserved.Background: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience. Methods: The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics. Results: The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined. Conclusions: A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.info:eu-repo/semantics/publishedVersio