Clinical and experimental rheumatology最新文献

Objectives: To evaluate the effectiveness and safety of anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1, on systemic lupus erythematosus (SLE) at a German academic tertiary care centre in a real-life setting.

Methods: We evaluated disease activity, clinical course and adverse events in a single-centre prospective observational cohort study of 26 SLE patients at baseline, 3, 6, 9, 12, 18 and 24 months of anifrolumab treatment. The decision to initiate therapy was made according to current guidelines (EULAR 2024).

Results: There was a significant reduction in the disease activity indices SLE-Disease Activity Index 2000 (SLEDAI-2k) (6.0±3.9 vs. 2.8±2.6, p≤0.001) and European Consensus Lupus Activity Measurement Index (ECLAM) (1.92 ±1.16 vs. 0.94±0.99, p=0.001) after just three months of treatment. After 12 months, definition of remission in SLE (DORIS) was achieved in 53% of patients and lupus low disease activity state (LLDAS) in 89% of patients. Mucocutaneous manifestations responded quickly and there were significant improvements in fatigue and arthritis/arthralgia. A favourable response was also seen in patients who had received previous therapies or after long duration of the disease. This was accompanied by a reduction in the glucocorticoid dose. Overall, the drug was safe and well tolerated.

Conclusions: In our real-world experience, anifrolumab achieved sustained remission after just 3 months of treatment and a significant reduction in disease activity in most patients. These data suggest that SLE patients with active disease benefit from anifrolumab therapy regardless of prior therapies or disease duration.

Objectives: Autoimmune diseases (ADs) are chronic inflammatory disorders characterised by systemic or organ-specific immune hyperactivation. Ultrasound (US), a radiation-free, cost-effective, and operator-friendly imaging modality, holds significant potential for clinical management of ADs. This study aims to map the global research landscape of US in ADs through bibliometric analysis.

Methods: English-language articles and reviews were retrieved from the Web of Science Core Collection. CiteSpace was used for cluster analysis and burst detection of research; VOSviewer generated co-occurrence networks; Biblioshiny R package visualised contributions by countries, institutions, authors, journals, citations, and keywords.

Results: A total of 1333 publications (2008-2024) were analysed. France emerged as the leading contributor in influence metrics, with Assistance Publique-Hôpitaux de Paris as the central collaborative hub. Key researchers included Craig Sable, Andrea Beaton, and Emmy Okello. Core journals were Echocardiography-a Journal of Cardiovascular Ultrasound and Allied Techniques and Clinical and Experimental Rheumatology. Current research priorities focus on rheumatic heart disease (RHD) and rheumatoid arthritis (RA), while glandular and intestinal ultrasonography show emerging potential.

Conclusions: Over the past 16 years, US has demonstrated versatile roles in ADs, validating its clinical utility. Future priorities include reducing the disease burden of RHD and advancing precision medicine in RA through US-guided strategies.

Objectives: To assess risk factors for rethrombosis, the intensity and maintenance of anticoagulation in primary antiphospholipid syndrome (APS).

Methods: We retrospectively included 81 patients with thrombotic APS under VKAs with ≥4 INR determinations per year in at least 1 year. We defined an index period as the time between the first available INR value and the next thrombotic event, or the time between the first and last available INR if rethrombosis-free. We recorded demographic and clinical/serologic variables, mean INR, mean INR-AUC, and anticoagulation intensity (INR<2.5, INR 2.5-3.5, and INR>3.5). For the statistical analysis we used Cox survival analysis, hazard function (H(t)) curves and AUC.

Results: The median follow-up time was 6.4 years. 64 patients had no rethrombosis, whereas 17 did (15 arterial, 2 venous). The risk factors for rethrombosis were number of previous rethrombosis (RR 7.3 95% CI 2.3-322.7, p=0.007) and INR intensity (RR 0.03, 95% CI 0.002-0.367, p=0.001). Results were similar when only arterial events were analysed. At the H(t) curves, the cumulative risk was higher in patients with an INR <2.5 than those in an INR of 2.5-3.5. A mean INR of 2.2 identified patients at risk of rethrombosis (SE=0.82, SP=0.20, AUC=0.42).

Conclusions: The number of previous thrombotic events and the intensity of anticoagulation are rethrombosis risk factors. An INR ranging 2.5-3.5 protects against re-thrombosis, including arterial events.

Objectives: There is a limited number of studies comparing paediatric to adult antiphospholipid syndrome (APS) patients. Our objective was to analyse the characteristics of patients presenting with antiphospholipid antibody (aPL)-related clinical manifestations during childhood versus adulthood.

Methods: We retrieved baseline characteristics from an international registry of persistently aPL-positive adult patients. Clinical events were grouped as vascular and non-vascular. We compared the frequency of and the timeline between vascular and non-vascular events for different age groups at the time of their first aPL-related manifestations: a) paediatric- (0-17 years) versus adult-onset (18-75 years); and b) based on narrower age intervals. Secondly, we analysed the timeline between the first aPL-related clinical event and first aPL positivity.

Results: Of 787 patients, 447 (57%) had only vascular events, 108 (14%) only non-vascular events, and 232 (29%) both. Compared to adult-onset patients (n=742), paediatric-onset patients (n=45) presented more commonly with a non-vascular event (49% vs. 19%, p=0.0001). The percentage of patients presenting with a non-vascular event mostly decreased with each increasing age group. Timeline analysis demonstrated 317 (40%) patients had a positive aPL test within the same calendar year (c-y) of the first clinical event, 207 (26%) within 1 to 3 c-y, and 263 (33%) more than 3 c-y.

Conclusions: Our analysis of an international registry for persistently aPL-positive patients demonstrates that patients with paediatric-onset aPL-related manifestations more commonly present with non-vascular events. These results highlight the importance of understanding the clinical differences between paediatric and adult APS patients, which have diagnostic, therapeutic, and research implications.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disease that characterised by persistent synovial joints inflammation, which ultimately results in progressive joint destruction and significant disability. Ineffective drug treatment for severe arthritis can lead to significant physical disability and a marked decline in quality of life. Recent research has significantly advanced our understanding of the underlying molecular mechanisms of RA, which leads to the emergence of novel immunotherapeutic strategies that provide patients with a broader range of treatment options. This review aims to synthesise the current knowledge of the molecular mechanisms of RA, related signalling pathways, and the latest immunotherapy approaches, including biologic agents, targeted small molecules, and novel therapies.Furthermore, we will discuss the efficacy and safety profiles of these therapies, analyse pressing issues in contemporary research, and explore future directions in the field.

Objectives: To investigate the use of anti-infective prescriptions (AIPs) in axial spondyloarthritis (axSpA) patients treated with tumour necrosis factor α inhibitors (TNFi) therapy and determine factors associated with increased risk of anti-infective use.

Methods: In this nationwide matched cohort study, we extracted information on all adult biologic-naive patients with axSpA initiating treatment with a TNFi in 2003-2018 from ICEBIO. Each patient was matched on age, sex, and calendar time to five individuals from the general population. AIPs were collected from nationwide registers two years before and after TNFi initiation. Prescription incidence rates (IR) were calculated, and multivariable analysis was conducted.

Results: The study identified data on 378 axSpA patients. The axSpA patients had higher IR per patient-year (py) of AIPs than comparators (1.12 (1.04-1.20) vs. 0.40 (0.38-0.42), p<0.001) before TNFi treatment. After TNFi initiation, the IR per py of AIP increased to 1.43 ((1.35-1.52), p<0.001), with a significant increase for antibiotics (1.04 (0.97-1.12) to 1.29 (1.21-1.38), p<0.001) and antivirals (0.03 (0.2-0.04) vs. 0.07 (0.06-0.1), p<0.001). Prior AIPs, female sex, and higher HAQ score were associated with increased AIPs after TNFi initiation, while age, smoking, and the use of glucocorticoids or methotrexate were not.

Conclusions: Filled AIPs among axSpA patients increased after TNFi initiation in contrast to what has been documented in prior studies on severe infections. This indicates an increase in non-severe infections or a lower threshold for AIPs among physicians after treatment initiation. Furthermore, axSpA patients were prescribed more AIPs before TNFi treatment compared to the general population, suggesting elevated baseline infection risk.

Objectives: The aim of the study was to investigate changes in alexithymia scores upon fibromyalgia (FM) treatment.

Methods: This prospective observational cohort study was conducted at the Istanbul Physical Medicine and Rehabilitation Training and Research Hospital. Patients diagnosed with fibromyalgia syndrome (FM) according to American College of Rheumatology criteria were included. All participants received duloxetine treatment, combined aerobic exercise. FM symptoms were assessed using Visual Analog Scale (VAS) at baseline and at 6 months, while alexithymia was evaluated using Toronto Alexithymia Scale-20 (TAS-20) at baseline, 3, and 6 months. Statistical analysis included repeated measures ANOVA with Greenhouse-Geisser correction, paired t-tests, and correlation analyses, with adjustments for age, BMI, and daily medication count.

Results: A total of 100 patients completed the study. VAS scores significantly decreased from the baseline (mean ± SD: 7.4±1.2) to 6 months (4.1±1.3; p<0.001). TAS-20 total scores also showed significant reductions at 3 months (57.8±7.6) and 6 months (54.2±7.1) compared to the baseline (61.5±7.9; p<0.001). Improvements in TAS-20 scores was correlated with reductions in VAS scores (r=0.41, p=0.002).

Conclusions: Combined duloxetine treatment and aerobic exercise could significantly improve both alexithymia symptoms and pain levels in FMS patients over a six-month period. Higher baseline alexithymia scores were associated with greater improvements in both alexithymia and pain symptoms, suggesting that patients with more severe initial alexithymia may benefit more from this treatment.

Clinical trial no: NCT06841302, registration date: 2025-02-18. (https://www.clinicaltrials.gov/).

Objectives: Whipple's disease (WD) is a rare systemic chronic infection with a large diagnostic delay that favours immunomediated complications. Rheumatological symptoms mimicking rheumatological conditions (RC) usually appear first. However, prevalence of WD among patients with RC is still unknown, therefore, we aimed to study the prevalence of WD in a rheumatological setting and identify clinical/laboratory parameters that detect RC patients at high risk of WD.

Methods: Data of 23,094 patients attending a rheumatological outpatient clinic between 6/2019 and 8/2023 were retrospectively analysed. Clinical features of WD patients in this cohort were compared with a separate retrospective cohort of 55 WD patients for validation.

Results: Due to unsatisfactory response to disease-modifying anti-rheumatic drugs (DMARDs) and/or development of gastrointestinal/systemic symptoms, 38 patients were referred for duodenal biopsy and WD was diagnosed in 6/38. Thus, prevalence of WD was 6/23,094 (0.03%, 95% CI 0.01-0.06%). Considering patients with a clinical suspicion of WD, prevalence rose to 6/38 (15.78%, 95% CI 6.02-31.25%), and over 20% in males (5/21, 23.81%, 95% CI 8.22-47.2%). Interestingly, at diagnosis, erythrocyte sedimentation rate and C-reactive protein were elevated in all patients with WD. This finding was confirmed in the separate cohort of 55 patients with WD.

Conclusions: WD is rare but in a rheumatological setting its prevalence is much higher than expected. Physicians should be aware of this condition and investigate its presence to reduce diagnostic delay, unnecessary DMARDs and risk of complications. Correct interpretation of clinical picture, including erythrocyte sedimentation rate and C-reactive protein, is the key to reach this diagnosis.