Predictors of musculoskeletal flares and Jaccoud׳s arthropathy in patients with systemic lupus erythematosus: A 5-year prospective study

Objective To investigate the prognostic value of US in predicting musculoskeletal flares and Jaccoud׳s arthropathy (JA) in systemic lupus erythematosus (SLE). Methods A total of 80 out of 94 patients (76 female; age 45.5 ± 13.2 years) with non-deforming non-erosive (NDNE) arthritis and 48/60 healthy controls (42 female; age 49.6 ± 11.6 years) completed the 5-year follow-up study. Each patient was prospectively assessed for the occurrence of musculoskeletal flares using BILAG2004 and hand deformities according to Jaccoud׳s articular index. Baseline clinical, serological, semi-quantitative (0–3 scale) ultrasound (US) findings, PD-synovitis and PD-tenosynovitis scores were used as covariates to identify predictors of study outcomes. Short Form 36 v2 (SF36v2) health survey questionnaire was administered. Results Overall, 12 MS flares in 10 (12.5%) patients were recorded and the incidence rate was 3.0 per 100 patient-year. Baseline PD-synovitis score independently predicted MS flare (p < 0.001; RR = 2.0; 95% CI: 1.4–3.0) within 2 years since US examination. In all, 5 (6.2%) patients developed JA whose incidence rate was 1.25 per 100 patient-year. Independent risk factors for development of JA were higher longitudinal BILAG score in the musculoskeletal domain (p = 0.005; RR = 2.4; 95% CI: 1.3–4.6) and longer disease duration (p = 0.013; RR 1.2; 95% CI: 1.1–1.3). JA and active musculoskeletal inflammation (BILAG ≥ C), but not US erosions, were associated with lower results in SF36v2 physical and mental summary components. Conclusions Performing musculoskeletal US can be useful in order to predict MS flares. Jaccoud׳s deformities may arise in patients with long-standing SLE and prolonged, even subclinical, joint and tendon inflammation

Ultrasonographic assessment of bone erosions in the different subtypes of systemic lupus erythematosus arthritis: Comparison with computed tomography

Background: The aim was to determine the accuracy of high-resolution ultrasonography (US) for detecting erosion in the metacarpophalangeal (MCP) and wrist joints of patients with different subtypes of systemic lupus erythematosus (SLE) arthritis, using computed tomography (CT) as the gold-standard reference method. Method: The ulnar head, radiocarpal and second to fifth MCP joints in 26 patients with SLE - 9 classified as having rhupus syndrome, 10 as having Jaccoud's arthropathy (JA) and 7 as having non-deforming non-erosive (NDNE) arthritis - were subdivided into areas and bilaterally evaluated for the presence of bone erosion by CT and US. On CT, erosion volume was scored according to the outcome measures in rheumatology-rheumatoid arthritis magnetic resonance imaging (OMERACT-RAMRIS) score. On US, erosions were semi-quantitatively scored 0-3 according to scoring by ultrasound structural erosion (ScUSSe) systems. Results: Erosions were detected by CT in 92/728 areas (12.6 %) and by US in 43/728 areas (5.9 %). Sensitivity, specificity and accuracy of US overall was 36 %, 98 % and 90 % compared with 57 %, 98 % and 93 % in the dorsal and lateral aspects of the second and fifth MCP, which were identified as areas with the best US reliability. Adding wrist joints would capture a larger number of erosions without affecting the accuracy. US detected 90.0 % of CT erosions with bone volume loss >20 % and 51.2 % of erosions with bone volume loss >10 %. Patients with rhupus had a greater number of larger erosions than those with JA or NDNE arthritis, with prevalent involvement of the MCP joints. Overall reliability of US in detecting bone erosions was moderate for rhupus syndrome (0.55) and JA (0.58), but poor for NDNE arthritis (0.10). Conclusion: US had moderate sensitivity and excellent specificity for detection and semi-quantitative assessment of bone erosions in SLE

Long-term glucocorticoid treatment and high relapse rate remain unresolved issues in the real-life management of polymyalgia rheumatica: a systematic literature review and meta-analysis

A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR).Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5&nbsp;years were respectively 77% (95%CI 71-83%), 51% (95%CI 41-61%), and 25% (95CI% 15-36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1&nbsp;year from treatment initiation was 43% (95%CI 29-56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR.This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies. Key Points: • High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years. • A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR. • Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results. • Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies

Assessment Of Circulating Endothelial Cells And Their Progenitors As Potential Biomarkers Of Disease Activity And Damage Accrual In Behçet's Syndrome

PURPOSE: To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behçet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. PATIENTS AND METHODS: CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behçet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. RESULTS: The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. CONCLUSION: Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS

Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus

IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined. MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s). ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients' sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients' sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-&amp; beta;2-glycoprotein-I (a &amp; beta;2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies. ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include &amp; beta;2GPI

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials

Background Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. Methods STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)–European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). Findings Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47–2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). Interpretation In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response

Telemedicine in rheumatology: high specificity and sensitivity of follow-up virtual video consultations during COVID-19 pandemic

To evaluate the reliability of virtual video-assisted visits, added to the tight control strategy for inflammatory rheumatic diseases (IRDs), in identifying patients that need treatment adjustment