RMD Open最新文献

Objective: Recent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries.

Methods: A total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS).

Results: Individuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits.

Conclusions: Our findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies.

Objectives: Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.

Methods: In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.

Results: Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.

Conclusion: Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.

Trial registration number: NL8900.

Objectives: To develop and validate a web-based ecological momentary assessment (EMA) tool to enhance symptoms monitoring among patients with Sjögren's disease (SjD).

Methods: Consecutive adults with SjD were enrolled in this pilot observational study. Participants used the WebApp over a 3-month period, for the daily collection of individual EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) scales and separate assessment of eyes and mouth dryness, using 0-10 numerical scales. Primary outcome was the measure of the interdaily variability of symptoms. Data collected through the WebApp were compared with those obtained with paper-based questionnaires administered during a final visit, using distinct approaches (predicted error, maximum negative error and maximum positive error). User experience was assessed using the System Usability Scale (SUS) score.

Results: Among the 45 participants, 41 (91.1%) were women. Median age was 57 years (IQR: 49-66). Daily variability of symptoms ranged between 0.5 and 0.8 points across the scales. Over the 3-month period, the predicted error ranged between -1.2 and -0.3 points of the numerical scales. The greatest differences were found for fatigue (-1.2 points (IQR: -2.3 to -0.2)) and ESSPRI score (-1.2 points (IQR: -1.7 to -0.3)). Over the last 2 weeks, the predicted error ranged between - 1.2 and 0.0 points. Maximum negative error ranged between -2.0 and -1.0 points, and maximum positive error between -0.3 and 0.0 points. Median SUS score was 90 (IQR: 85-95).

Conclusion: Our results demonstrate the usability and the relevance of our web-based EMA tool for capturing data that closely reflects daily experiences of patients with SjD.

Rational: Studies are needed to determine if multimorbidity screening and management reduce the rate of multimorbidity accumulation in patients with chronic inflammatory rheumatic diseases (IRD).

Objectives: This study evaluates the impact of systematic screening programme on patient care and hospitalisation rates.

Methods: Patients with IRD who participated in the screening programme (exposed patients) were identified within the French national health database and matched with controls. Two sets of analysis were performed: one with multivariate analysis and a second using a propensity score matching to ensure comparability between exposed patients and controls. The primary endpoint (PE) was a composite score assessing the dispensation of multimorbidity-preventing drugs, including vaccines, lipid-lowering agents, antiosteoporotic medications and antiplatelet drugs, during the year following the index date.

Results: The first analysis included 286 exposed patients and 858 controls, demonstrating a higher rate of meeting the PE in exposed patients (adjusted OR=1.6 (1.2-2.2), p<0.01). Propensity score matching resulted in 281 exposed patients and 281 controls. Exposed patients exhibited a significantly higher rate of meeting the PE compared with controls (54.8% vs 44.5%; OR=1.5; p=0.015), with increased utilisation of vaccines, cholesterol-lowering drugs and antiosteoporotic medications. Furthermore, emergency admission and hospitalisations for fracture, cardiovascular events or infection were significantly less frequent in the exposed group (7.1% vs 15.3%; OR=0.42, p<0.01), with a reduction in severe infections (0.7% vs 3.9%; p=0.03).

Conclusion: Systematic multimorbidity screening in patients with IRD boosted preventive medication use and reduced hospital admissions, justifying time and resource allocation for screening.

Objectives: Although joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our understanding of differences and similarities regarding forefoot involvement between ACPA-positive and ACPA-negative rheumatoid arthritis (RA) at diagnosis. Therefore, we (1) compared metatarsophalangeal (MTP) joint counts, walking disabilities and inflamed tissues between ACPA groups and (2) studied associations of joint swelling/tenderness and walking disabilities with underlying inflamed tissues within ACPA groups.

Methods: 171 ACPA-positive and 203 ACPA-negative consecutively diagnosed patients with RA had a physical joint examination (swollen joint count-66/tender joint count-68), filled a Health Assessment Questionnaire including the domain walking and underwent MRI of the MTP joints at diagnosis. Synovitis, tenosynovitis, osteitis and intermetatarsal bursitis (IMB) were assessed. Findings in age-matched healthy controls were applied to define abnormalities on MRI.

Results: While ACPA-negative RA patients had more swollen joints (mean SJC 8 vs 6 in ACPA-positives, p=0.003), the number of swollen MTP joints was similar (mean 1 in both groups); walking disabilities were also equally common (49% vs 53%). In contrast, inflamed tissues were all more prevalent in ACPA-positive compared with ACPA-negative RA. Within ACPA-positive RA, IMB was associated independently with MTP-joint swelling (OR 2.6, 95% CI 1.4 to 5.0) and tenderness (OR 3.0, 95% CI 1.8 to 5.0). While in ACPA-negatives, synovitis was associated independently with MTP-joint swelling (OR 2.8, 95% CI 1.4 to 5.8) and tenderness (OR 2.5, 95% CI 1.3 to 4.8). Tenosynovitis contributed most to walking disabilities.

Conclusions: Although the forefoot of ACPA-positives and ACPA-negatives share clinical similarities at diagnosis, there are differences in underlying inflamed tissues. This reinforces that ACPA-positive and ACPA-negative RA are different entities.

Objectives: To follow up four previously identified classes 'pure axial spondyloarthritis' (axSpA) ('axial'), 'axSpA with peripheral signs' ('inflammatory back pain+peripheral'), 'axSpA at risk' and 'no spondyloarthritis' ('no SpA'). They reflect the expert-opinion-free construct or 'Gestalt' of chronic back pain suspicious of axSpA. The aim was to assess participants' transitions between these classes over time.

Methods: Participants with chronic back pain of ≤2 years duration, suspicious of axSpA from the SPondyloArthritis Caught Early cohort were analysed. Latent class (LCA) and latent transition analysis (LTA) using clinical, laboratory and imaging data at baseline and 2 years were calculated. Conditional and marginal probabilities were obtained, reflecting the probability of a spondyloarthritis feature in a class and the probability of the participant's class membership, respectively. Transitional probabilities were extracted revealing potential switches across classes. The analyses were performed in all participants using imputations for missing data and in participants with full data at baseline and 2 years.

Results: Baseline and 2 years LCA models were constructed for 702 participants, resulting in the same four-class model as previously described. LTA revealed only a 3% transition from the 'no SpA' to the 'at-risk' class from baseline to 2 years with all other participants remaining in their initially assigned class. Sensitivity analysis on 384 participants with complete data at both baseline and 2 years showed similar results, underlining the model's robustness.

Conclusions: Transitions between the four classes over 2 years were basically inexistent, highlighting the unlikelihood of developing new class-defining features of axSpA after an initial clinical workup.

In rheumatoid arthritis (RA), the identification of prognostic factors (PF) capable of predicting disease outcome, response to treatment or success of dose reduction is an important issue, as these factors are intended to serve as a basis for decision-making. The task is complex from the outset, as the definition of disease prognosis or therapeutic prognosis is not uniquevocal. The heterogeneity of the definitions used partly explains the failure to identify PF that can be applied at an individual level. But other factors also contribute. First, the scope of the disease studied is too broad, including nosologically different entities. Second, potential PF are only measured at a single point of time, whereas changes over a period of time should be taken into account to a greater extent, not forgetting the potential impact of the treatment received during this period. Beyond these limiting factors, one of the main obstacles to the identification of PF is probably the fact that the phase of the disease is not sufficiently taken into account. Predicting the disease outcome when it is well established is a more complex challenge than when it is just beginning, as many factors are likely to interfere. The same applies to therapeutic PF, which should be determined according to disease duration. Difficulties also arise from the approaches used, which are often restricted to a single field of interest whereas they should be much more integrative and call on new large-scale data analysis tools with a view to precision medicine.In RA, prognosis can be defined at two levels: disease outcome, including joint damage and risk of extra-articular manifestations and/or complications, and treatment outcome, including response to therapy, risk of adverse effects and drug-free remission.

Objective: To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) with different histological patterns of inflammation: transmural inflammation (TMI) and inflammation limited to adventitia (ILA), compared with normal TABs from patients without GCA.

Methods: Expression of 770 immune-related genes was profiled with the NanoString nCounter PanCancer Immune Profiling Panel on formalin-fixed paraffin-embedded TABs from 42 GCA patients with TMI, 7 GCA patients with ILA and 7 non-GCA controls.

Results: Unsupervised clustering of the samples revealed two distinct groups: normal TABs and TABs with ILA in one group, 41/42 TABs with TMI in the other one. TABs with TMI showed 31 downregulated and 256 upregulated genes compared with normal TABs; they displayed 26 downregulated and 187 upregulated genes compared with TABs with ILA (>2.0 fold changes and adjusted p values <0.05). Gene expression in TABs with ILA resembled normal TABs although 38 genes exhibited >2.0 fold changes, but these changes lost statistical significance after Benjamini-Yekutieli correction. Genes encoding TNF superfamily members, immune checkpoints, chemokine and chemokine receptors, toll-like receptors, complement molecules, Fc receptors for IgG antibodies, signalling lymphocytic activation molecules, JAK3, STAT1 and STAT4 resulted upregulated in TMI.

Conclusions: TABs with TMI had a distinct transcriptome compared with normal TABs and TABs with ILA. The few genes potentially deregulated in ILA were also deregulated in TMI. Gene profiling allowed to deepen the knowledge of GCA pathogenesis.

Objective: Fibromyalgia syndrome (FMS) is characterised by widespread pain and is associated with mood disorders such as depression as well as poor sleep quality. These in turn have been linked to increased risk of suicidal ideation. Clinical guidelines generally do not recommended opioids in FMS, but they are routinely prescribed to a considerable proportion of FMS patients. We assessed the association of long-term opioid prescription for FMS with risk of depression, sleep disorders and suicidal ideation, when compared with short-term opioid use.

Methods: Retrospective cohort study combing several population-wide databases covering a population of five million inhabitants, including all adults who received an initial opioid prescription from 2014 to 2018 specifically prescribed for FMS. We examined the occurrence of depression, sleep disorders or suicidal ideation outcomes in patients with an initial long-term opioid prescription (>90 days) versus those who received a short-term treatment (<29 days). We employed multivariable Cox regression modelling and inverse probability of treatment weighting based on propensity scores and we performed several sensitivity analyses.

Results: 10 334 patients initiated short-term (8309, 80.40%) or long-term (2025, 19.60%) opioids for FMS. In main adjusted analyses, long-term opioid use was associated with an increased risk for depression (HR: 1.58, 95% CI 1.29 to 1.95) and sleep disorder (HR: 1.30, 95% CI 1.09 to 1.55) but not with suicidal ideation (HR: 1.59, 95% CI 0.96 to 2.62). In models assessing outcomes since day 90, an increased risk for suicidal ideation was observed (HR: 1.76, 95% CI 1.05 to 2.98).

Conclusion: These findings suggest that continued opioid use for 90 days or more may aggravate depression and sleep problems in patients with FMS when compared with patterns of short-term treatment.