This study aims to assess the risks of primary and second primary keratinocyte cancers (KCs) in patients with rheumatoid arthritis (RA) and in relation to treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs. Nationwide cohort study of patients treated with Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitor (TNFi), or non-TNFi bDMARDs, using data from the Swedish Rheumatology Quality Register linked to other registers including the National Cancer Register, 2012 through 2023. Adjusted hazard ratios (HRs) were estimated via Cox regression using TNFi as reference. We identified 21,756 unique patients with RA. Based on 155 incident KC with JAKi, 458 with non-TNFi and 766 with TNFi, the HR for JAKi vs TNFi was 1.39 (1.16-1.68), corresponding to 1 extra KC case per every 244 patients per year. For non-TNFi vs TNFi, the HR was 0.96 (0.86-1.08). By subtype, the HR for JAKi vs TNFi was 1.41 (1.13-1.75) for basal cell carcinoma and 1.49 (1.09-2.05) for squamous cell carcinoma (SCC). For abatacept vs etanercept, the HR for SCC was 1.48 (1.11-1.97). The HR for a second primary KC was 1.31 (0.94-1.82) for JAKi and 0.94 (0.75-1.17) for non-TNFi bDMARD vs TNFi. Patients treated with JAKi have an elevated risk of KC compared with patients treated with TNFi. Although the class of non-TNFi bDMARDs is not associated with increased KC risk, we repeated a drug-specific signal of increased risk for SCC with abatacept.

No app-based nonpharmacological intervention has yet demonstrated to meaningfully improve disease activity, functional status, and disease-specific quality of life in axial spondyloarthritis (axSpA). We evaluated Axia, a CE-marked smartphone application designed for axSpA, that combines personalised exercise therapy, patient education, and disease management, supported by gamification for long-term adherence. To evaluate its clinical efficacy, a 12-week monocentric randomised controlled interventional trial was conducted involving 200 patients with axSpA with stable pharmacotherapy. Patients were randomised (1:1) to either using Axia (intervention group [IG]) or standard of care (control group [CG]). A total of 186 participants (mean age 50.61 years, 66% females, 56% with radiographic axSpA, mean Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 5.17, and 58% received biologicals or Janus kinase inhibitors) completed the study (95 in the IG and 91 in the CG). Compared to CG, participants in the IG demonstrated significant improvements in BASDAI (analysis of covariance [ANCOVA]-estimated group difference: -1.508, P < .001), Bath Ankylosing Spondylitis Functional Index (-1.139; P < .001), and Ankylosing Spondylitis Quality of Life questionnaire (-2.297; P < .001), all exceeding minimal clinically important difference thresholds. A significantly higher proportion of patients in the IG achieved an Assessment of Spondyloarthritis International Society (ASAS)20 response compared to the CG (51% vs 9%; P < .001), and the ASAS40 response rate was also higher (23% vs 3%; P < .001). No concerning safety signals were observed. These findings support the potential of Axia as a safe and effective nonpharmacological intervention to further improve the state of care of patients with axSpA in addition to conventional anti-inflammatory pharmacotherapy.

Calcium pyrophosphate deposition (CPPD) disease is a common form of arthritis affecting older individuals. This disease is characterised by high levels of pyrophosphate in articular cartilage, resulting in calcium pyrophosphate crystal formation in humans and inflammatory and degenerative arthritis. A loss-of-function mutation in the TNFRSF11B locus (also known as CCAL1), which encodes osteoprotegerin (OPG) causes familial CPPD. OPG acts as a decoy receptor for RANKL, thereby inhibiting osteoclast differentiation and activity. CPPD currently lacks any animal models. The goal of this study was to develop a murine model of early CPPD by incorporating the TNFRSF11B gene mutation in mice and determining its effects on bones, joints and CPPD biomarkers. We used CRISPR/Cas9 editing to generate mice carrying the TNFRSF11B mutation (Opgmt). Joint and bone phenotypes, bone remodelling biomarkers and key CPPD biomarkers were assessed in wild type (WT; Opgwt/wt), Opgwt/mt and Opgmt/mt mice at 6 and 12 months of age. Male and female mice carrying Opgmt displayed osteopenia and high bone remodelling markers at 6 and 12 months of age. This phenotype was concurrent with increased osteoclast numbers and activity. Female Opgmt/mt mice also displayed significant osteoarthritis features by 12 months of age, including articular cartilage loss in the lateral compartment of the knee based on Mankin structural damage scores. Additionally, biomarkers pathognomonic of CPPD disease, such as pyrophosphate, transforming growth factor (TGF)-β1 levels and ENPP1 activity, were significantly elevated in the joints of both 6- and 12-month-old female mice with OPGmt. Mice carrying Opgmt display bone and joint phenotypes characteristic of early-stage CPPD disease in humans. Opgmt mice represent a novel preclinical model of early CPPD, ideal for exploring potential therapies targeting the disease prior to the development of major joint damage.

This study aims to provide an update of the European Alliance of Associations for Rheumatology (EULAR) rheumatoid arthritis (RA) management recommendations addressing the most recent insights. An International Task Force was formed with a wide expertise and solicited 2 systemic literature research activities on the safety and efficacy of disease-modifying antirheumatic drugs (DMARDs). New evidence was discussed, considering the update from 2022. A voting process was applied to each item. Levels of evidence and strengths of recommendation were assigned, and participants voted on the levels of agreement. The task force agreed on 5 overarching principles and reduced the number of recommendations to 9 concerning use of conventional synthetic DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b)DMARDs (tumour necrosis factor inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab, including biosimilars) and targeted synthetic [ts]DMARDs (namely the Janus kinase inhibitors [JAKi] tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target), and tapering following clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were considered. Initially, MTX ideally in combination with short-term GCs is recommended; upon insufficient response after 3 to 6 months, a bDMARD should be added; after careful consideration of risks, including MACEs, malignancies and/or thrombo-embolic events, JAKi may also be considered. If the first bDMARD (or JAKi) fails, any other bDMARD (from another or the same class) or JAKi (considering risks) is recommended. With sustained remission, DMARDs may be tapered, but caution is required as stopping often leads to a flare. Levels of evidence and levels of agreement were high for most recommendations. These updated EULAR recommendations provide consensus on RA management based on currently available evidence regarding efficacy, safety, and cost.

Tenosynovitis is a key imaging feature in the preclinical phase of rheumatoid arthritis. Prior studies suggest that presence of magnetic resonance imaging (MRI) tenosynovitis may better predict future clinical arthritis than MRI synovitis. We hypothesised that the volume of subclinical inflammation within tendon sheaths may explain this association in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals. This study sought to assess whether MRI-derived tenosynovitis (TSV) and joint synovitis (SV) volumes predict inflammatory arthritis (IA) in anti-CCP-positive individuals without clinical synovitis, beyond clinical/serological markers. We included 223 anti-CCP-positive individuals with musculoskeletal symptoms without clinical synovitis. All underwent baseline contrast-enhanced MRI of the hand and wrist. TSV and SV were quantified via manual segmentation and three-dimensional (3D) reconstruction (OsiriX-MD). IA progression was defined as ≥1 clinically swollen joint. Cox regression and receiver operating characteristic (ROC) analyses were performed. Of 223 participants, 67 (30%) developed IA over a median 13.3-month follow-up. Inter-reader agreement for volumetric scoring was excellent (intraclass correlation coefficient > 0.90 across all regions). Baseline tenosynovitis (34.5%) was associated with progression (P < .001). TSV was higher in progressors than non-progressors (1607 vs 705 mm³, P = .003), remained predictive after adjusting for SV (P = .008), and outperformed SV in ROC analysis (area under curve (AUC) = 0.697 vs 0.582). In multivariable analysis, TSV (P < .001) and tender joint count (P = .014) independently predicted progression beyond clinical and serological markers. Higher total inflammation volume correlated with shorter time to progression (P = .008). MRI-derived TSV independently predicts IA and outperforms SV. Quantitative TSV assessment may enhance risk stratification and support preventive strategies in at-risk individuals.