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Background: IL6-related T cell activation and TNFaα-dependent cell proliferation are major targets of therapy in the RA synovium. We investigated whether expression of these pathways in RA synovial biopsies is associated with disease activity and response to therapy. Method: Correlation and gene set enrichment studies were performed using gene expression profiles from RA synovial biopsies. Immunostaining experiments of GADD45B and PDE4D were performed on independent additional sets of early untreated RA samples, obtained in two different centers by needle-arthroscopy or US-guided biopsies. Results: In 65 RA synovial biopsies, transcripts correlating with disease activity were strongly enriched in TNFaα-induced genes. Out of the individual variables used in disease-activity scores, tender joint count, swollen joint count and physician's global assessment, but not CRP or patient's global assessment displayed a similar correlation with the expression of TNFaα-dependent genes. In addition, TNFaα-induced genes were also significantly enriched in transcripts over-expressed in synovial biopsy samples obtained from poor-responders to methotrexate or tocilizumab, prior to initiation of therapy. GADD45B (induced by TNFaα in monocytes) and PDE4D (induced by TNFaα in FLS) immunostaining was significantly higher in overall poor-responders to therapy in 46 independent baseline samples obtained from early untreated RA patients prior to initiation of therapy. GADD45B (but not PDE4D) immunostaining was significantly higher in the sub-group of patients with poor-response to methotrexate therapy, and this was confirmed in another population of methotrexate-treated patients. Conclusion: Higher expression of TNFaα-induced transcripts in early RA synovitis is associated with higher disease activity, and predicts poor response to first-line therapy. That over-expression of TNFaα-induced genes predicts poor-response to therapy regardless of the drug administered, indicates that this molecu, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL). Methods Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed. Results A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab. Conclusion Open-label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.

La prise en charge de la polyarthrite rhumatoïde (PR) a connu ces dernières années une évolution remarquable avec l’avènement de thérapeutiques ciblées très efficaces. Ces traitements ont pu être développés grâce à une connaissance plus précise de la physiopathologie de la polyarthrite en 2016. Dans les années futures, l’analyse de l’inflammation du tissu synovial sur le plan histologique et moléculaire permettra aux cliniciens de mieux définir le traitement de la PR., [Synovial biopsy: an essential tool for guiding rheumatoid arthritis treatment?] Over the last years, the management of rheumatoid arthritis (RA) has been largely improved owing to the introduction of biologicals. These agents have been developed based on a better understanding of the disease pathophysiology. In the next years, the histopathological and molecular features of the synovial tissue will likely help clinicians better define RA treatment strategies.

Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East.

Scores on the Health Assessment Questionnaire (HAQ) predict the need for support measures in patients with rheumatoid arthritis (RA). In this study we compare the performance of the HAQ in this context with that of the more disease-specific Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire.

OBJECTIVES: Biological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of administration affects patients' treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients' appreciation. Thus, the Belgian Be-raise survey aimed to examine whether RA patient's experience of their current biological treatment coincided with the treating physician's perception. METHODS: A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient's perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient. RESULTS: Completed questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored ≥ 9) than that of the treating physician (35%), regardless of the route of administration (p< 0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician´s perception of patient's satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p< 0.001). CONCLUSIONS: Patients' satisfaction with biological treatment is high, but there is a considerable mismatch between patients´ and rheumatologists´ appreciation on the route of administration of biological therapy in RA. Physi

OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries. RESULTS: The estimated off-label use of RTX in Europe was 0.5%-1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. CONCLUSIONS: RTX use for SLE in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted.

OBJECTIVES: Fatigue is a major complaint of patients with systemic lupus erythemasosus (SLE). While several studies have demonstrated the benefits of exercise, the effects of supervised training were never compared to those of home training. METHODS: Forty-five SLE patients suffering from fatigue, as defined by Krupp's fatigue severity scale (FSS) ≥ 3.7, were randomized in 3 groups: supervised training group (STG), home training group (HTG), and control group (CG). Primary outcome was the change in FSS at month 3. In parallel, we measured the physical working capacity measured at 75% of the predicted maximal heart rate (PWC75%/kg) and the modified Borg's scale to assess perception of exertion. RESULTS: Both STG and HTG, but not the CG, statistically improved their FSS at month 3. By contrast, the PWC75%/kg and the Borg's scale did not improve in none of the groups. Surprinsingly, compliance was similar and low (±50%) in both exercise groups. Moreover, less compliant patients improved their fatigue as much as more compliant patients. CONCLUSIONS: Patients included in the STG and the HTG similarly improved their fatigue, irrespectively of their level of compliance, raising the possibility that the beneficial effect on fatigue was not only exercise-related.

La fasciite à éosinophiles est une entité rare décrite pour la première fois par Shulman en 1974 et localisée préférentiellement aux portions distales des membres. L’IRM est l’examen d’imagerie de choix aussi bien pour le diagnostic que pour le suivi de cette affection. La forme classique typique en IRM se caractérise par une atteinte exclusive des fascias, mais il peut exister de façon moins fréquente des anomalies de signal des tissus musculaires et de la graisse hypodermique adjacents aux fascias. Les diagnostics différentiels du syndrome de Shulman en IRM sont nombreux et variés parmi les affections des tissus mous superficiels et profonds.

OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

Objective: There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We utilized data from the Euro-Lupus Nephritis Trial (ELNT) to evaluate the performance of proteinuria, serum creatinine (SCr), and urine red blood cells (RBCs) as predictors of good long-term renal outcome. Methods: ELNT subjects with measures of proteinuria, SCr, and urine RBCs at 3, 6 or 12 months and a minimum 7 year follow-up were included (n=76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as SCr ≤ 1.0mg/dL) at 7 years. Receiver operating characteristic (ROC) curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters; sensitivity and specificity were calculated for the parameters alone and in combination. Results: Proteinuria of <0.8g/day 12 months after randomization was the single best predictor of good long-term renal function (sensitivity=81%, specificity=78%). The addition of SCr to proteinuria did not improve performance; addition of urine RBCs significantly decreased sensitivity to 47%. Conclusions: This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome. Inclusion of urine RBCs as part of a composite outcome measure actually undermines the predictive value of the trial data. We therefore suggest that urine RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. This article is protected by copyright. All rights reserved.

Eosinophilic fasciitis is a rare condition. It is generally limited to the distal parts of the arms and legs. MRI is the ideal imaging modality for diagnosing and monitoring this condition. MRI findings typically evidence only fascial involvement but on a less regular basis signal abnormalities may be observed in neighboring muscle tissue and hypodermic fat. Differential diagnosis of eosinophilic fasciitis by MRI requires the exclusion of several other superficial and deep soft tissue disorders.

Our hypothesis was that preserved cartilage in osteoarthritic (OA) joints is thicker compared to non-OA joints. We took the femorotibial joint as a model. First, we determined that Computed Tomography arthrography (CTA) is the imaging modality with the highest sensitivity and interobserver agreement for the detection of cartilage surface lesions. Second, we analyzed sources of interobserver disagreement for the grading of cartilage at CTA. Third, we identified a target area of cartilage that is frequently preserved in knee OA until late stages of the disease, at the posterior aspect of the medial condyle. Finally, we showed that cartilage thickness at the posterior aspect of the medial condyle is increased in OA knees compared to non-OA knees, and that this thickening is correlated to the grade of OA., (MED - Sciences médicales) -- UCL, 2015

BACKGROUND: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). METHODS: Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). RESULTS: After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. CONCLUSIONS: In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. TRIAL REGISTRATION NUMBER: NCT00204022.