RMD Open最新文献

Objectives: To investigate the therapeutic potential of caspase-1 inhibition in systemic lupus erythematosus (SLE) and lupus nephritis (LN) using the MRL-Fas^lpr mouse model.

Methods: Female Murphy Roths large (MRL)-Fas^lpr mice were treated with a caspase-1 inhibitor (pralnacase) or sham treatment from 2.5 to 5.5 months of age. Disease progression was assessed through analysis of systemic and renal parameters, including proteinuria, blood urea nitrogen, kidney histopathology and immune cell infiltration. Cytokine expression and caspase activity were measured to elucidate the mechanism of action. Additional experiments with interleukin (IL)-1 receptor antagonist and pancaspase inhibition treatment as well as post-disease onset intervention were conducted.

Results: Caspase-1 inhibition significantly reduced systemic inflammation, lymphadenopathy and skin lesions in MRL-Fas^lpr mice. Treated mice exhibited decreased proteinuria, improved renal function and reduced kidney pathology. The treatment specifically targeted caspase-1 activity, leading to decreased IL-18 levels as well as attenuated immune cell activation and infiltration in the kidneys. Selective caspase-1 inhibition showed comparable results with pancaspase inhibition. IL-1 receptor antagonist treatment did not significantly affect disease progression, suggesting IL-18 as the primary driver of pathology. Post-disease onset intervention with caspase-1 inhibition also showed efficacy, although to a lesser extent than pre-onset treatment.

Conclusions: Caspase-1 inhibition effectively ameliorates both systemic and renal manifestations of SLE in MRL-Fas^lpr mice, primarily through suppression of IL-18-mediated inflammation. This study identifies caspase-1 as a promising therapeutic target for SLE and LN, warranting further investigation in clinical trials.

Background/purpose: Social media (SM) has become an indispensable tool in healthcare, providing platforms for networking and education. However, its use presents challenges including misinformation, professional boundaries and platform-specific limitations. Building on the EULAR EMEUNET survey, we aimed to characterise SM utilisation within rheumatology globally.

Methods: The EULAR study group on social media (SoMeR) designed a 30-item survey, which was validated, translated into six languages and distributed via mailing lists and SM channels of EMEUNET, PANLAR Joven, AFLAR and APLAR Young Rheumatology. Analysis employed Human Development Index (HDI) and Internet Freedom Index (IFI) to assess digital divides.

Results: Among 597 respondents from 59 countries (42.2% female), 92.3% used SM professionally. Female professionals demonstrated significantly higher SM use (94.4% vs 88.8%, p=0.02). Knowledge acquisition was the primary driver (73.0%), with 67.2% using SM for academic research updates. SM adoption varied regionally (Europe 97.3% vs Asia-Pacific 88.6%). Lower HDI regions reported more connectivity issues (28.1% vs 16.7%), while higher HDI cited legal restrictions (24.4%). Countries with restricted internet freedom paradoxically reported higher positive SM impact (4.04/5 vs 3.86/5, p<0.01).Cross-cohort analysis (2015-2023) revealed trends toward professional applications and away from networking functions. Over half (56.9%) reported feeling overwhelmed by SM content, particularly in South America and Africa (73.3%/70.3%, p<0.01). Interest in digital communication was high (83.3%), with webinars being the preferred format (41.1%).

Conclusions: This survey demonstrates SM's integral role in rheumatology with significant regional variations, calling for targeted interventions addressing connectivity and legal concerns while maintaining professionalism and scientific integrity.

Background: Cognitive impairment (CI) is one of the most common manifestations of neuropsychiatric systemic lupus erythematosus (SLE). This study aimed to characterise the course of CI over a 1-year period in patients with SLE and its associated factors.

Methods: 175 adult SLE patients from the University of Toronto Lupus Clinic were assessed at baseline, 6 months and 12 months using the American College of Rheumatology Neuropsychological Battery. CI was classified based on standardised z-scores in cognitive domains. Patients were categorised as persistent-CI (CI at all three time-points; T0, T1 and T2), never-CI (no CI at any time-point) or fluctuating-CI (CI at 1-2 assessments). Sociodemographic, clinical, laboratory and medication data were collected at each visit. Patients with persistent-CI were compared with never-CI patients. CI severity was determined based on the mean z-score of tests across all six domains.

Results: Over 1 year, 46% of patients experienced CI, with 17% showing persistent-CI, 29% fluctuating-CI and 54% never-CI. Persistent-CI patients exhibited more severe CI compared with fluctuating-CI. The most frequently affected cognitive domains were learning and memory, simple attention and processing speed, and visual-spatial construction. Factors associated with CI persistence over 1 year included Black race, older age at SLE diagnosis, divorced/separated status at T0 and higher disease-related damage at T0.

Conclusion: This study highlights the variable nature of CI in SLE patients, with most exhibiting a stable course over 1 year. Factors such as sociodemographic characteristics and comorbidities may influence CI persistence.

Objective: Androgen deprivation therapy (ADT) for prostate cancer (PCa) induces bone loss and increases fracture risk, yet baseline bone mineral density (BMD) assessment is rarely performed. Opportunistic BMD evaluation using routine imaging could improve osteoporosis screening in this population. We aimed to assess the feasibility of using trabecular attenuation (TA) in Hounsfield units (HU) from the low-dose CT component of 18F-fluorocholine (FCh) positron emission tomography (PET)/CT for opportunistic osteoporosis and vertebral fracture screening in men with PCa, compared with stand-alone diagnostic CT.

Methods: In this retrospective single-centre study, 81 patients with PCa who underwent both FCh-PET/CT and stand-alone CT within 6 months were included. TA(HU) was measured at L1-L3 vertebral levels on both scans. ADT exposure and duration were recorded to assess their associations with TA. Primary outcomes were intraclass correlation coefficients (ICC) and Bland-Altman agreement between TA values from FCh-PET/CT and stand-alone CT. Secondary outcomes included associations between TA, ADT duration and vertebral fractures.

Results: TA values from FCh-PET/CT and stand-alone CT were comparable (ICC: 0.72, 0.70 and 0.67, for L1-L3; p<0.001). Mean FCh-PET/CT TA were 121 HU (L1), 122 HU (L2) and 118 HU (L3). Lower attenuation correlated with longer ADT duration (r=-0.43; p=0.008). Vertebral fractures were observed in 18.5% of patients and were associated with lower TA (87.8 vs 127.5 HU; p=0.01).

Conclusions: FCh-PET/CT provides a feasible, readily available approach for opportunistic osteoporosis and fracture risk screening in men with PCa, supporting its integration into routine imaging workflows to promote bone health assessment and fracture prevention.

Objective: This multicentre randomised controlled trial aimed to compare the efficacy and safety of iguratimod (IGU) and hydroxychloroquine (HCQ) in patients with active primary Sjögren's syndrome (pSS).

Methods: Eligible pSS patients were randomised 1:1 to receive IGU (25 mg two times per day) or HCQ (0.2 g two times per day) for 24 weeks. The primary endpoint was the Sjögren's Syndrome Responder Index-30 (SSRI-30) response rate at week 24. Secondary endpoints included the Sjögren's Tool for Assessing Response (STAR), European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and biomarker changes.

Results: A total of 78 pSS patients were randomised (40 in HCQ group, 38 in IGU group) and 66 patients (35 in HCQ group, 31 in IGU group) completed the 24-week research. SSRI-30 response rate, the primary endpoint, was numerically higher in the IGU group (57.9% vs 40.0%, p=0.114), but with no statistical significance. However, IGU demonstrated significantly higher response rates for key secondary endpoints including STAR (39.5% vs 15.0%, p=0.015) and ESSDAI (21.1% vs 5.0%, p=0.034) response rate. IGU also showed superior IgG reduction (p=0.046). Adverse events were more frequent with IGU (60.6% vs 37.8%) but were mostly mild.

Conclusion: IGU monotherapy demonstrated significant improvements in composite, systemic and serologic outcomes compared with HCQ in active pSS and was well-tolerated. These findings establish IGU as a promising therapeutic option for pSS, particularly in the subset of patients with hyperglobulinaemia.

Trial registration number: NCT04981145.

Background: Sacroiliac joint (SIJ) MRI is commonly used in diagnosing spondyloarthritis (SpA). Current Assessment of SpondyloArthritis International Society (ASAS) recommendations on reporting SIJ MRIs in patients with known or suspected axial SpA recommend always stating whether bone marrow oedema (BME), erosions and fat lesions are present/absent and whether the MRI is compatible with axial SpA.

Purpose: To investigate if routine care radiologists already report what has now been recommended and to assess the agreement between local radiologists and central SpA experts.

Materials and methods: This study includes retrospective interpretation of images acquired in routine care. Patients diagnosed with SpA enrolled in a clinical registry in one of five European countries involved in the EuroSpA Collaboration, with an available SIJ MRI and an associated local MRI report, were included. MRIs were read centrally by two readers, who registered global features (eg, MRI indicative of SpA), and various inflammatory and structural lesions as present/absent. Similar information was extracted from local reports. Findings were analysed with descriptive statistics.

Results: Overall, 913 patients (40 years±13, 492 men) were included. In 24%, the local MRI reports stated whether the MRI was overall indicative of SpA or not. Presence/absence of BME, erosions and fat lesions was mentioned in 88%, 48% and 29% of local reports, respectively. Inflammatory lesions were more often reported as present by local than central readers (46% vs 36%), and structural lesions less often (33% vs 50%).

Conclusion: This study demonstrated a large gap between the clinical practice of reporting SIJ MRIs and recent reporting recommendations.

Background: Janus kinase inhibitors (JAKi), like baricitinib, are used as monotherapy (MONO) and in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients. This study aimed to evaluate the long-term efficacy, drug survival and safety of baricitinib MONO versus combination therapy (COMBO) in a prospective cohort of patients with RA.

Methods: We analysed data from 219 RA patients initiating baricitinib in a single-centre, prospective observational cohort between 2017 and 2023. Clinical data, patient-reported outcomes and safety events were collected every 3 months. Drug survival was analysed using the Kaplan-Meier method, and longitudinal outcomes were assessed using linear mixed-effects models.

Results: The cohort included 219 patients (165 MONO, 54 COMBO) with high baseline disease activity (mean DAS28-ESR 4.0). Both groups showed rapid and sustained clinical improvement, with disease activity stabilising in the low range by 6 months of treatment. One third of the patients (n=72, 33%) achieved Boolean remission, with no significant difference between groups (p=0.35). Median drug survival was 36 months and was similar for both regimens (log-rank p=0.82). Discontinuation due to adverse events occurred in 10.9% of patients. Four thrombotic events were noted, all in patients with pre-existing cardiovascular risk factors, with no new safety signals emerging.

Conclusions: In this real-world cohort, baricitinib demonstrated sustained long-term effectiveness, drug survival and an acceptable safety profile. The similar outcomes observed for MONO and COMBO indicate that baricitinib may be used effectively as MONO in patients with RA for whom MTX is not suitable or tolerated.

Objectives: To compare the efficacy of ozoralizumab in patients with rheumatoid arthritis (RA), with or without large joint involvement (LJI).

Methods: A post hoc analysis was conducted for Japanese patients with RA who received ozoralizumab 30 mg every 4 weeks for 52 weeks in the previous OHZORA (with concomitant methotrexate) and NATSUZORA (without concomitant methotrexate) randomised trials. Patients were subgrouped by LJI, defined as the presence of swelling in the shoulder, elbow, knee or ankle. Disease activity, physical dysfunction, blood inflammatory marker levels and progression of joint destruction during treatment were examined.

Results: The numbers of patients included were 152 for the OHZORA trial (111 with LJI, 41 without LJI) and 94 for the NATSUZORA trial (72 with LJI, 22 without LJI). The completion rates of both trials did not differ significantly between the patient groups. Baseline Clinical Disease Activity Index scores were significantly higher in patients with LJI than in those without LJI, but this difference was not present as early as day 3 of ozoralizumab treatment and at most subsequent assessments. A similar trend was observed for patient-reported/physician-reported outcomes and Health Assessment Questionnaire. Blood interleukin-6 and matrix metalloproteinase-3 levels in patients with LJI continuously decreased during treatment. Changes in modified Total Sharp Score at week 24 were similar between the groups in the OHZORA trial.

Conclusion: Ozoralizumab has the potential to improve disease activity and physical dysfunction and prevent joint destruction in patients, regardless of the presence of LJI, and is a reasonable treatment option, even for patients with LJI.

Trial registration number: jRCT2080223971 and jRCT2080223973.

Objective: To characterise phenotype and functional profibrotic M2 markers in circulating monocytes and cultured monocyte-derived macrophages (MDMs) from systemic sclerosis (SSc) patients (pts) with progressive interstitial lung disease (ILD) (prog-ILD), non-progressive ILD (no-prog-ILD) and without ILD (no-ILD).

Methods: Fifty-five SSc pts and 20 age-matched healthy controls were evaluated. In 36 SSc pts, circulating monocytes expressing toll-like receptor-4 (TLR4, M1 marker) and M2 phenotype markers (CD204, CD206, CD163) were detected by flow cytometry. Moreover, MDMs of 29 SSc pts were analysed by quantitative real-time PCR and Western blotting for gene expression and protein synthesis with regard to the production of profibrotic mediators: transforming growth factor-ß1 (TGFß1), Mer tyrosine kinase receptor (MerTK) and arginase-1 (ARG1). Interleukin-6 and 4 (IL6, IL4), as well as C-C motif chemokine ligand 2 and 18 (CCL2/MCP1 and CCL18) from culture medium, were evaluated by enzyme-linked immunosorbent assay (ELISA).

Results: Prog-ILD SSc pts showed a higher percentage of TLR4⁺CD204⁺CD206⁺CD163⁺ monocytes versus no-prog-ILD, and significantly higher compared with no-ILD SSc pts.Interestingly, MDMs from prog-ILD SSc pts showed a significantly higher gene expression and protein synthesis of TGFβ1, and a significantly higher protein synthesis of MerTK, CD206, IL4 and CCL18 compared with no-prog-ILD SSc pts. Finally, gene expression and protein synthesis of TGFβ1, TLR4, CD206, CD163, ARG1, MerTK and IL6 were significantly increased in prog-ILD SSc versus no-ILD SSc MDMs.

Conclusions: Cultured MDMs from circulating monocytes in SSc pts with prog-ILD show markedly increased profibrotic biomarkers and mediator expression, indicating an enhanced fibrotic phenotype compared to non-prog and no-ILD SSc pts.