Clinical and experimental rheumatology最新文献

Objectives: Clonal haematopoiesis of indeterminate potential (CH), somatic genetic mutations conferring stem cells selective advantage, are associated with increased inflammatory cytokine production, cardiovascular disease (CVD), and malignancy. We investigated whether CH was related to risk of rheumatoid arthritis (RA), an inflammatory autoimmune disease.

Methods: Within the UK Biobank, we studied 186,577 unrelated individuals with baseline data collection, genome-wide genotyping, whole exome sequencing (WES) read for CHIP, and linked general practice (GP) data for identification of incident RA in follow-up. We excluded those with prevalent RA or taking RA medications at baseline. We tested for associations between variant allele fraction (VAF) >2% and >10% for the 8 most common CHIP mutations in the general population, and incident RA, identified by billing code algorithms. Cox regression models estimated hazard ratios (HR, 95% confidence interval) for incident RA.

Results: 594 participants developed incident RA over median follow-up 7.1 years (IQR 6.4-8.0); median time to RA was 3.9 years (IQR 2.0-5.6). Incident RA cases were slightly older at enrolment, more likely to be female, have smoked, have higher body mass index (BMI), and have prevalent CVD, and hypercholesterolaemia at baseline. However, there was no difference in the presence of CHIP mutations at baseline; 6.3% vs. 6.4% of those who did and did not develop incident RA in follow-up had any CHIP mutation at >2% VAF.

Conclusions: Common CHIP mutations, including TET2, TP53, and SF3B1 mutations, were not associated with risk of incident RA when restricted to those with most complete general outpatient and hospital record follow-up in the UK Biobank.

Objectives: A randomised controlled trial (RCT) demonstrated that a single 6 mL intra-articular (IA) injection of polyacrylamide hydrogel (iPAAG) provided comparable efficacy and safety to hyaluronic acid over one year in patients with moderate-to-severe knee osteoarthritis (OA). This study reports the longer-term outcomes of iPAAG.

Methods: In this long-term extension of the RCT (ClinicalTrials.gov Identifier: NCT04045431), participants treated with IA 2.5% iPAAG were followed for changes from the RCT baseline in WOMAC pain, stiffness, and physical function subscales (0-100), as well as patient global assessment (PGA) of OA impact. Safety was monitored throughout the extension study.

Results: Of 119 participants initially treated with iPAAG, 91 (47 men) entered the extension, and 58 completed 5 years of follow-up. At year 5, WOMAC pain improved by a mean of -16.2 points (95% CI: -20.0 to -12.4; p<0.0001). Similar improvements were observed across other WOMAC domains and PGA. Between years 1 and 5, 79 adverse events (AEs) were reported in 47 participants (51.6%), none considered related to iPAAG.

Conclusions: A single IA injection of iPAAG was associated with sustained improvements in pain and function, with a favourable safety profile maintained through 5 years. These observational data support iPAAG as a promising long-acting, non-surgical treatment option for knee OA.

Objectives: Romosozumab (ROMO) is a monoclonal antibody targeting sclerostin (SOST), a key regulator of bone metabolism. It has been demonstrated that changes in SOST levels can affect distinct niches within the bone marrow that support haematopoiesis. This study investigated the effect of ROMO on complete blood count (CBC) parameters.

Methods: We conducted a 12-month prospective observational study in post-menopausal women with severe osteoporosis treated with ROMO 210 mg/monthly over one year between October 2023 and April 2025. CBC values were assessed at baseline, 6 and 12 months. Absolute changes in CBC were assessed with a mixed model for repeated measures.

Results: A total of 113 women (mean age of 73.4±9.7 years) were included. Neutrophils levels slightly decreased over time, with a significant decrease at 6 months (p=0.022), that was not sustained at 12 months (p=0.500). Haemoglobin and lymphocytes levels showed no significant differences over the period of the study. In the overall trend across time points, there was a statistically significant decrease in the neutrophil-to-lymphocyte ratio (NLR) over the 12 months (2.0 ± 1.1 at baseline, 1.8 ± 1.1 at month 6, and 1.8 ± 1.2 at month 12; p=0.034), with a small effect size (Cohen's δ = 0.22).

Conclusions: In post-menopausal women with severe osteoporosis, 12 months of ROMO treatment was associated with a statistically significant reduction in NLR, reflecting a potential modulation of systemic inflammation, though the clinical relevance of this modest shift remains uncertain and warrants further investigation.

Objectives: We investigated the diagnostic and prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA).

Methods: In this single-centre observational study, 61 patients with MPA who underwent high-resolution computed tomography (HRCT) and 18F-FDG PET/CT were included. ILD diagnosis was based on HRCT. 18F-FDG uptake in the lung parenchyma was assessed as a binary variable (present/absent). Diagnostic performance was evaluated by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The prognostic value was determined by Δ (1-year-baseline; positive=improvement) in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) using multivariable linear regression models.

Results: 18F-FDG uptake showed high specificity and PPV (both 1.00) but limited sensitivity (0.63) and NPV (0.26) for ILD detection. Patients with 18F-FDG uptake demonstrated significantly greater Δ in FVC (β=8.26 [2.87-13.64], p=0.004) and DLCO (β=7.38 [0.06-14.69], p=0.048) compared with those without uptake. The prognostic value of 18F-FDG uptake was greater than that of the ILD pattern determined by HRCT (usual interstitial pneumonia [UIP] vs. non-UIP). While non-UIP patterns were associated with favourable Δ in FVC (β=8.02 [0.66-15.38], p=0.034), they were not associated with significant changes in DLCO (β=0.66 [-8.83-10.16], p=0.885).

Conclusions: 18F-FDG PET/CT demonstrated high specificity but limited sensitivity for detecting ILD in MPA, limiting its use as a screening tool. However, given its prognostic value, 18F-FDG PET/CT could be considered as a complementary imaging modality may aid prognostic stratification in MPA-associated ILD.

Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by the involvement of multiple targets. Accumulating evidence suggests the key role played by T helper (Th)9 and Th17 cells in PsA. Recently, the ability to activate GITR in promoting differentiation and proliferation of Th17 and Th9 cells has been investigated in several inflammatory conditions. We aimed to evaluate the effects of GITR/GITRL interaction in the immune responses underlying the disease, including the main PsA target sites.

Methods: Twenty-one PsA patients with active disease, naive to disease-modifying anti-rheumatic drugs, were enrolled. Peripheral blood mononuclear cells and synovial fluid (SF) mononuclear cells were collected to assess GITR and GITRL expression by flow cytometry. An in vitro functional assay with recombinant GITR agonist was performed to detect the effect on T cell subsets. Synovial and ileal biopsies were obtained to evaluate GITR and GITRL expression by immunofluorescence. Healthy subjects and osteoarthritis patients were enrolled as controls.

Results: We reported an increased in vitro expression of GITR among CD4+ T cells and its cognate ligand GITRL on antigen-presenting cells in PsA peripheral blood. In vitro, the addition of the GITR agonist resulted in increased expansion of Th9 and Th17 cells. Increased expression of GITR and GITRL was found even in PsA SF, synovium and ileum.

Conclusions: Our results suggest a novel role of GITR/GITRL in promoting the expansion of Th9 and Th17 in PsA-inflamed tissues.

Objectives: The primary objective of the study was to evaluate the efficacy and safety of the monoclonal antibody AK111 in participants with active ankylosing spondylitis (AS).

Methods: Adult participants who met the Modified New York Criteria for Ankylosing Spondylitis revised in 1984 were randomly assigned to the AK111 75 mg, 150 mg, 300 mg group or placebo group with the ratio of 1:1:1:1. Each participant received 5 subcutaneous (SC) injections of the study drug (week 0/1/4/8/12). The primary efficacy endpoint of this study was the percentage of participants who reached the Assessment of SpondyloArthritis International Society (ASAS) 20 response at week 16. The key secondary endpoint was the percentage of participants who reached the ASAS 40 response at week 16.

Results: A total of 125 participants were randomly enrolled in this study. The ASAS 20 response rates at week 16 in the AK111 75 mg, 150 mg, and 300 mg groups were 80.6%, 71.9%, and 66.7%, respectively, each of which was higher than the placebo group (37.5%). The overall response rate of ASAS 40 in the AK111 group was also better than the placebo group. The incidence rate of treatment emergent adverse events (TEAEs) after receiving AK111 75 mg, 150 mg, 300 mg, and placebo group was 93.5% (29/31), 75.0% (24/32), 73.3% (22/30), and 75.0% (24/32), respectively; the incidence of drug-related AEs was 58.1% (18/31), 50% (16/32), 50% (15/30) and 43.8% (14/32), respectively. The majority of the TEAEs were grade 1 and 2 in severity. No neutralising antibody positivity was found during the study.

Conclusions: The humanised monoclonal antibody AK111 was safe and well tolerated in treating AS and showed a good efficacy by improved ASAS 20/ASAS 40 response.