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Mashup Score: 12
Objective To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Results At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically hi
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Mashup Score: 7EULAR points to consider for patient education in physical activity and self-management of pain during transitional care - 22 day(s) ago
Objectives A EULAR task force was convened to develop points to consider (PtC) for patient education in physical activity and self-management of pain in young people with juvenile-onset rheumatic and musculoskeletal diseases during transitional care. Methods A task force of 26 people from 10 European countries followed the EULAR Standardised Operating Procedures to establish overarching principles (OAPs) and PtC based on a literature review and expert consensus. Level of evidence (LoE), grade of recommendation (GoR) and level of agreement (LoA) were determined. Results Two OAPs and seven PtC were formulated. The OAPs highlight the importance of personalised transitional care in rheumatology, ideally based on shared decision-making and incorporate interactive education to empower young individuals in managing their physical activity and pain. The PtC emphasise the clinical importance of patient education in these areas to improve readiness to transfer from paediatric to adult care. For
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Mashup Score: 6Shared lung and joint T cell repertoire in early rheumatoid arthritis driven by cigarette smoking - 22 day(s) ago
Objectives Smoking has been associated with an increased risk of developing rheumatoid arthritis (RA) in individuals carrying shared epitope (SE) HLA-DRB1 alleles. Yet, little is known about the regional and systemic T cell dynamics of smoking and a potential link to T cell infiltration in inflamed synovia. In this study, we, therefore, sought to study T cell features in lung and inflamed joints in smoking versus non-smoking patients. Methods We set up a framework to monitor T cells in paired bronchoalveolar lavage fluid, blood and inflamed synovium tissue samples from 17 new-onset treatment naïve anticitrullinated protein antibody+RA patients. T cell receptor (TCR) repertoire of index-sorted tissue residing in T cells was determined by single-cell TCR sequencing coupled with deep immunophenotyping. Results A significant enrichment of CD4+ and CD8+ T cells was seen in synovial samples from smoking versus non-smoking patients, along with an increase in expanded T cell clonotypes. This w
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Mashup Score: 6Shared lung and joint T cell repertoire in early rheumatoid arthritis driven by cigarette smoking - 23 day(s) ago
Objectives Smoking has been associated with an increased risk of developing rheumatoid arthritis (RA) in individuals carrying shared epitope (SE) HLA-DRB1 alleles. Yet, little is known about the regional and systemic T cell dynamics of smoking and a potential link to T cell infiltration in inflamed synovia. In this study, we, therefore, sought to study T cell features in lung and inflamed joints in smoking versus non-smoking patients. Methods We set up a framework to monitor T cells in paired bronchoalveolar lavage fluid, blood and inflamed synovium tissue samples from 17 new-onset treatment naïve anticitrullinated protein antibody+RA patients. T cell receptor (TCR) repertoire of index-sorted tissue residing in T cells was determined by single-cell TCR sequencing coupled with deep immunophenotyping. Results A significant enrichment of CD4+ and CD8+ T cells was seen in synovial samples from smoking versus non-smoking patients, along with an increase in expanded T cell clonotypes. This w
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Mashup Score: 2
Objectives To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting. Methods In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi). Results Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those start
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Mashup Score: 67Expert consensus recommendations for the diagnosis and treatment of chronic non-bacterial osteitis (CNO) in adults - 25 day(s) ago
Background There is considerable practice variation in labelling, diagnosis and treatment of adults with sterile bone inflammation. We developed a expert consensus recommendations on the disease definition, diagnosis and treatment of this rare condition. Methods Systematic literature review and Grading of Recommendations, Assessment, Development and Evaluations-based appraisal of evidence, two Delphi surveys and three digital and in-person consensus meetings with a multidisciplinary expert panel and patient representatives. Results A consensus disease definition was developed and the term ‘chronic non-bacterial osteitis’ (CNO) is proposed to describe adults with sterile bone inflammation. For initial imaging evaluation of adults with suspected CNO, the panel recommends MRI or otherwise CT combined with nuclear imaging. Whole-body imaging at initial evaluation can be considered for diagnostic and prognostic purposes. Suggested first-line treatment in adults with active CNO includes non-
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Mashup Score: 17Pharmacodynamics of the S1P1 receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE - 28 day(s) ago
Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by autoreactive T and B lymphocytes. Sphingosine-1-phosphate (S1P) is involved in lymphocyte egress from peripheral lymphoid organs into the circulation. In phase 2a clinical trial, the potent, selective S1P1 receptor modulator cenerimod reduced circulating antibody-secreting cells and interferon (IFN)-associated biomarkers. Objectives Pharmacodynamic effects of 2 and 4 mg cenerimod were evaluated in the phase 2b clinical trial (CARE) in moderate to severe patients with SLE ([NCT03742037][1]). Methods Blood samples were collected at baseline and after 6 months of treatment with cenerimod or placebo from CARE. The gene expression signatures for type 1 interferon (IFN-1), IFN-γ and plasma cells were used to assess dose-dependent pharmacodynamic effects of cenerimod. Cell-type deconvolution was performed to estimate cell abundance. Results Cenerimod 4 mg reduced IFN-associated protein and gene sign
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Mashup Score: 1
Objectives To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting. Methods In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi). Results Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those start
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Mashup Score: 42
Objectives Belimumab is a putative disease-modifying agent in systemic lupus erythematosus (SLE), yet the molecular underpinnings of its effects and the ability to predict early clinical response remain unexplored. To address these, we undertook a longitudinal, in-depth blood transcriptome study. Methods RNA-sequencing was performed in the blood of active SLE patients at baseline and following 6 months of belimumab treatment (n=45 paired samples). Clinical response was determined according to the SLE Responder Index (SRI)-4 and Lupus Low Disease Activity State (LLDAS). Weighted correlation network analysis (WGCNA) was used to uncover gene module trait associations. Reversibility of SLE susceptibility and severity gene signatures was assessed. Machine learning was used to build models predictive of response. Results Belimumab induced widespread transcriptome changes with downregulation of pathways related to B cells, type I/II interferon, IL-6/STAT3 and neutrophil activation. These effe
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Mashup Score: 111
Objectives To explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE). Methods The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group an
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What is new on the treatment of #rheumatoid #arthritis? Check out the latest trial on #Ivarmacitinib (JAK1 oral inhibitor): ▶️ better ACR response at week 24 ▶️ sustained response through 52 weeks ▶️ manageable safety profile 🔗 https://t.co/ggac2C8Ryk https://t.co/uicsJ6FTn7