Arthritis Research & Therapy

BACKGROUND: Rheumatoid arthritis (RA) has a variable impact on different synovial joints, with inflammation being more commonly observed in some joints than others. Emerging evidence suggests that the anatomical variation in pathophysiology could result in differential responses to treatments across the joints, both within and between modes of action. This analysis aimed to characterize joint-specific responses to tofacitinib and methotrexate monotherapy in patients with RA. METHODS: This was a post hoc analysis of data from the phase III trial ORAL Start (NCT01039688), in methotrexate-naïve patients with RA...

OBJECTIVE: Studies evaluating the association of knee and hip osteoarthritis (OA) with falls and fractures have inconsistent findings. We aimed to investigate associations of symptomatic and radiographic knee and hip OA with risk of falls, recurrent falls, and fractures. METHODS: We conducted an electronic search of databases from inception to February 2023. Two authors independently screened studies, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale tool in eligible studies...

BACKGROUND: To compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept. METHODS: A 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart...

BACKGROUND: Physical function is an important determinant of health-related quality of life in radiographic axial spondyloarthritis patients (r-axSpA). To improve the basis of effective healthcare efforts, we aimed to investigate which demographic and disease-related factors that influence Bath Ankylosing Spondylitis Functional Index (BASFI) in r-axSpA patients overall and stratified by sex. Furthermore, we sought to explore differences between sexes regarding separate BASFI questions and also to explore which factors that may contribute to these differences...

BACKGROUND: Dimerization of the myeloid differentiation primary response 88 protein (MyD88) plays a pivotal role in the exacerbated response to innate immunity-dependent signaling in rheumatoid arthritis (RA). ST2825 is a highly specific inhibitor of MyD88 dimerization, previously shown to inhibit the pro-inflammatory gene expression in peripheral blood mononuclear cells from RA patients (RA PBMC). In this study, we elucidated the effect of disrupting MyD88 dimerization by ST2825 on the pathological properties of synovial fibroblasts from RA patients (RA SFs)...

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease and causes chronic pain and disability to the elderly. Several risk factors are involved, such as aging, obesity, genetic susceptibility, and environmental factors. We conducted a transcriptome-wide association study (TWAS) and chemical-related gene set enrichment analysis (CGSEA) to investigate the susceptibility genes and environmental factors. METHODS: TWAS analysis was conducted to identify the susceptibility genes by integrating the summary-level genome-wide association study data of knee OA (KOA) and hip OA (HOA) with the precomputed expression weights from the Genotype-Tissue Expression Project (Version 8)...

BACKGROUND: This work aims to develop a deep learning model, assessing atlantoaxial subluxation (AAS) in rheumatoid arthritis (RA), which can often be ambiguous in clinical practice. METHODS: We collected 4691 X-ray images of the cervical spine of the 906 patients with RA. Among these images, 3480 were used for training the deep learning model, 803 were used for validating the model during the training process, and the remaining 408 were used for testing the performance of the trained model...

OBJECTIVES: This study aimed to investigate the long-term effect of vitamin D supplementation compared to placebo over 5 years in participants with knee osteoarthritis (OA). We also aimed to describe the effect of maintaining sufficient serum vitamin D levels over five years in knee OA. METHODS: Participants (n = 173) from the Hobart centre of the Vitamin D Effects on Osteoarthritis (VIDEO) trial were extensively followed up 3 years after the cessation of 2-year investigational treatment...

BACKGROUND: Juvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying antirheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL)...

BACKGROUND: Synovial fibroblasts in rheumatoid arthritis (RAFLS) exhibit a pathological aberration of glycolysis and glutaminolysis. Henceforth, we aimed to investigate if dual inhibition of these pathways by phytobiological compound c28MS has the potential of synergistic therapy for arthritis by targeting both glucose and glutamine metabolism. METHODS: The presence of HK2 and GLS across various cell types and associated gene expression in human synovial cells and a murine model of arthritis was evaluated by scRNA-seq...

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare complication of primary Sjögren's syndrome (pSS). Several genes have proven to be associated with pSS and PAH. However, there is no study specifically addressing the genetic susceptibility in pSS combined with PAH. METHODS: Thirty-four unrelated patients with pSS-PAH were recruited from April 2019 to July 2021 at Peking Union Medical College Hospital. Demographic and clinical data were recorded in detail, and peripheral blood samples were collected for whole-exome sequencing (WES)...

BACKGROUND: While the availability of biological or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) has improved outcomes for rheumatoid arthritis (RA) patients, there remains a subset of individuals who fail to achieve low disease activity or remission despite multiple cycles of b/tsDMARDs. This state is referred to as 'difficult-to-treat (D2T)' RA. METHODS: Data from the Korean College of Rheumatology Biologics registry were utilized to analyze patients with RA who were treated with b/tsDMARDs...

OBJECTIVE: Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA...

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. METHODS: Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks...

BACKGROUND: Nail psoriasis is a common, physiologically, and psychologically disruptive, and yet often under-treated manifestation of psoriasis. The objectives of this analysis were to investigate the trajectory of nail psoriasis, a risk factor for psoriatic arthritis (PsA), with guselkumab vs adalimumab treatment followed by withdrawal, and determine characteristics associated with nail response in patients treated with guselkumab. METHODS: This post hoc analysis of the phase III trial VOYAGE 2 included patients with moderate-to-severe plaque psoriasis and baseline nail involvement...

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BACKGROUND: Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers. METHODS: We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers...

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease associated with aging, which often leads to joint stiffness and disability. Exercise is one of the most important non-pharmacological treatments and is prescribed as an indispensable treatment for OA. However, whether physical exercise is beneficial for preventing the progression of OA symptoms with age is poorly understood. We investigated the effects of exercise on spontaneously developed knee OA using male senescence-accelerated mouse prone 8 (SAMP8)...

BACKGROUND: Uncontrolled T-cell activation plays a key role in systemic sclerosis (SSc). Arsenic trioxide (ATO) has immunological effects and has demonstrated potential in preclinical SSc models. In this study, we assessed the efficacy of ATO in Fra2 transgenic (Fra2TG ) mice, which develop severe vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human SSc-associated pulmonary hypertension, therefore partially resembling to the SSc human disease...

BACKGROUND: Real-world studies assessing the comparative effectiveness of biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) as first-line targeted therapy are scarce. We analyzed the real-world persistence and effectiveness of etanercept (ETN), adalimumab (ADA), and Janus kinase inhibitors (JAKis) as first-line therapy in b/tsDMARD-naïve patients with rheumatoid arthritis (RA). METHODS: Adults (≥ 18 years) enrolled in the CorEvitas RA Registry and initiating ETN, ADA, or a JAKi (alone or in combination with csDMARDs) between November 2012 and June 2021 were included if they had 6 and/or 12 months' follow-up...