April 2024 to July 2024
Author: Bohdana Doskaliuk & Giovanni Fulvio
Annals of Rheumatic Diseases
Marrugo et al. (10.1136/ard-2024-225652) address the unclear role of metformin in preventing gout in individuals with pre-diabetes. The objective was to compare gout incidence in pre-diabetic adults starting metformin with those not using antidiabetic treatments. Using a propensity score-matched cohort study of 25,064 individuals, 1,154 metformin users were compared to 13,877 non-users. Over a median follow-up of 3.9 years, the incidence of gout was lower in metformin users (7.1 vs. 9.5 per 1000 person-years). Metformin use was associated with a 32% reduced risk of gout (HR 0.68, 95% CI 0.48 to 0.96), although no significant changes in serum urate or C-reactive protein were found.
Huang et al. (10.1136/ard-2023-225415) investigate endothelial cell (EC) dysfunction in systemic sclerosis (SSc), focusing on transcriptomic and epigenomic alterations. Single-cell RNA sequencing and chromatin analysis revealed that SSc arterial ECs showed increased apoptosis-related gene expression and elevated proangiogenic activities in tip and proliferating EC subpopulations. Altered intercellular signaling networks were linked to SSc pathology, including skin fibrosis and digital ulcers. ETS transcription factors (ELK4, ERF, and ETS1) were identified as key regulators of EC apoptosis and angiogenesis, offering potential therapeutic targets for addressing SSc-related vascular complications.
Baerwald et al. (10.1136/ard-2023-225414) aimed to evaluate the prevalence and predictive factors of severe persisting pain in rheumatoid arthritis (RA) patients despite treatment-controlled disease activity. Of 567 outpatients, 22.6% experienced persistent pain after 24 weeks. Persisting pain was significantly associated with higher levels of pain catastrophizing (p=0.002) and an increased number of tender joints (p=0.004). Neuropathic pain (NeP) was present in 26.5% of those with persisting pain, but baseline NeP scores were not predictive of persisting pain. These findings suggest that non-nociceptive pain, pain catastrophizing, and tender joints are key factors in persistent pain in RA.
Farisogullari et al. (10.1136/ard-2024-225869) examined the frequency and factors associated with disease flare in patients with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs) following SARS-CoV-2 vaccination. Among 7,336 patients, 3.7% experienced flares, and 1.6% required medication adjustments. Factors associated with increased flare risk included female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease (LDA OR=1.45, p<0.05; M/HDA OR=1.37, p>0.05), and cessation/reduction of antirheumatic medication (OR=4.76, 95% CI=3.44 to 6.58). Methotrexate (OR=0.57, 95% CI=0.37 to 0.90) and tumor necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) were associated with lower flare risk. Flares were uncommon overall.
Thiel et al. (10.1136/ard-2024-225587) explored the causes of prolonged B-cell depletion in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after rituximab (RTX) treatment. Deep phenotyping of 91 AAV patients’ peripheral and bone marrow B cells revealed reduced B-lymphoid precursors and delayed immature B-cell development. Post-RTX, a subset of patients showed impaired peripheral B-cell maturation, with low BAFF receptor expression leading to reduced B-cell survival. The findings suggest that impaired bone marrow B-lymphopoiesis and B-cell survival defects contribute to delayed B-cell recovery in AAV, influencing RTX retreatment schedules and post-therapy immunomonitoring.
Roberts et al. (10.1136/ard-2024-225585) investigated X chromosome inactivation (XCI) in females with systemic lupus erythematosus (SLE), a condition with a strong female bias. XCI, which silences one X chromosome, was analyzed in 181 female SLE cases, 796 controls, and 10 discordant twin pairs. Results showed significantly reduced XCI-skew in SLE patients compared to controls (p=1.3×10⁻⁵), with the effect strongest in those with severe disease. XCI-skew was seen in 6.6% of SLE cases versus 22% of controls and correlated with type I interferon-regulated gene expression. These findings suggest that XCI patterns in immune cells may be influenced by the disease state rather than predisposing factors.
This retrospective cohort study by Yoshimura et al. (10.1136/ard-2024-225914) assessed the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in 425 rheumatoid arthritis (RA) patients with chronic kidney disease (CKD), including those on haemodialysis. Over 36 months, drug retention rates were analyzed based on kidney function andbDMARD type. IL-6 inhibitors (IL-6is) had the highest retention rates, particularly in patients with an eGFR <30 mL/min/1.73 m² (HR 0.11, p=0.03), while TNFα inhibitors (TNFαis) showed lower retention in this group. All bDMARDs improved disease activity (DAS28-CRP/ESR) and reduced prednisolone dosage, with IL-6is showing superior efficacy and retention.
Kachler et al. (10.1136/ard-2023-224774) explored the role of aconitate decarboxylase 1 (Acod1) and its metabolite, itaconate, in osteoclast differentiation and bone loss in rheumatoid arthritis (RA). Itaconate levels were inversely correlated with RA disease activity. In Acod1-deficient mice, increased osteoclast numbers and bone erosion were observed, while treatment with itaconate derivative 4-OI reduced bone loss and osteoclast differentiation. Mechanistically, Acod1 inhibited osteoclast differentiation by regulating reactive oxygen species production and suppressing Hif1α-mediated aerobic glycolysis. These findings suggest that Acod1 and itaconate are key regulators of osteoclast function and bone degradation in RA-associated arthritis.
This randomized controlled study by Lend at al. (10.1136/ard-2024-226024) aimed to evaluate the association of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), and shared epitope (SE) with treatment responses to abatacept, certolizumab pegol, or tocilizumab compared to active conventional treatment (ACT) in early rheumatoid arthritis patients. In the NORD-STAR trial, 778 patients were randomized to various treatments. Abatacept showed a better response than ACT in RF/ACPA-positive patients at 24 weeks, but no significant differences were observed by 48 weeks. SE markers did not significantly enhance treatment predictions, and the genetic markers were not strong predictors of clinical outcomes.
Hu et al. (10.1136/ard-2024-225564) investigated the role of the enteric virome, specifically bacteriophages, in the development of rheumatoid arthritis (RA). Faecal samples from 30 pairs of RA patients and healthy siblings were analyzed via metagenomic sequencing to study virome diversity and virome-bacteriome interactions. Results showed that the composition of the enteric bacteriophageome was distorted in RA and correlated with immunological markers such as anti-CCP autoantibodies and HLA-DR shared epitopes. Bacteriophages, including Prevotella and Oscillibacter phages, were found to provoke autoimmune responses in CD4+ T cells via molecular mimicry, suggesting their potential involvement in RA pathogenesis.
Bohdana Doskaliuk, MD, PhD
Bohdana is an Assistant Professor at Ivano-Frankivsk National Medical University. Her PhD research focused on pulmonary involvement in systemic sclerosis and its potential correction. Bohdana actively contributes as a reviewer and editor. She serves as an Associate Editor for Rheumatology International and is an Editorial Board member for Therapeutic Advances in Musculoskeletal Disease and Rheumatology Advances in Practice. She is also affiliated with the European Academy of Allergy and Clinical Immunology and European Respiratory Society. Bohdana is a Country Liaison Sub-Committee member.
Giovanni Fulvio MD
Giovanni is currently a PhD student at the University of Pisa. His research is focused on salivary gland ultrasonography and the role of multi-modal imaging techniques in rheumatology, particularly in the diagnosis and management of Sjögren’s syndrome. He completed his fellowship at the Rheumatology Unit, University of Pisa, where he also serves as a tutor in salivary gland ultrasonography. Giovanni is actively involved in professional societies, being a member of the Società Italiana di Reumatologia, European Reference Network on Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) and of the EMEUNET Newsletter Sub-Committee.