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Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis.

ABSTRACT: BACKGROUND:The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). METHODS:This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. RESULTS:Data from 109 patients with a mean RA duration of 0.7?years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p?

SUBMITTER: Conaghan PG

PROVIDER: S-EPMC6805378 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis.

Conaghan Philip G PG Østergaard Mikkel M Troum Orrin O Bowes Michael A MA Guillard Gwenael G Wilkinson Bethanie B Xie Zhiyong Z Andrews John J Stein Amy A Chapman Douglass D Koenig Andrew A

Arthritis research & therapy 20191021 1

<h4>Background</h4>The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).<h4>Methods</h4>This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were ...[more]

PMID: 31639034

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Project description:To study clinical predictors for radiographic progression after 1?year in an early rheumatoid arthritis (RA) trial.In the SWEFOT trial population, disease modifying antirheumatic drug (DMARD) naïve RA patients started methotrexate; 3-month responders (DAS28 <3.2) continued (n=147), while non-responders were randomised to addition of sulfasalazine+hydroxychloroquine (n=130) or infliximab (n=128). X-rays were scored by the Sharp-van der Hejde score (SHS) method and radiographic progression was defined as a ?5 increase after 1?year. Potential baseline predictors of radiographic progression were tested using multivariable logistic regression, adjusted for potential confounders.79 of 311 patients with available radiographs at baseline and follow-up had radiographic progression. The following baseline parameters were independent predictors of radiographic progression at 1?year: baseline erosions (adjusted OR=2.29, 95% CI 1.24 to 4.24), erythrocyte sedimentation rate (adjusted OR per tertile increase=1.72, 95% CI 1.12 to 2.65) and C-reactive protein (adjusted OR per tertile increase=1.52, 95% CI 1.03 to 2.26). Current smoking was an independent predictor of radiographic progression (adjusted OR=2.17, 95% CI 1.06 to 4.45). These results remained after further adjustment for treatment strategy. Three-dimensional matrix including current smoking status, erosions and C-reactive protein tertiles showed a 12-63% risk gradient from patients carrying none compared with all predictors. Rheumatoid factor (RF)/anti-cyclic citrullinated peptide (anti-CCP) positivity did not significantly predict radiographic progression using SHS increase ?5 as cut-off. In a secondary exploratory analysis using cut-off >1, both RF and anti-CCP positivity were significant predictors in the unadjusted, but not the adjusted analyses. The other parameters also remained significant using this lower cut-off.In addition to previously described predictors, we identified smoking as a strong independent risk factor for radiographic progression in early RA.NCT00764725.

Project description:ObjectivesTo unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.Methods144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.ResultsCellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.ConclusionsWe demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

Project description:INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. METHODS: In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n?=?632) or had undifferentiated arthritis (UA) (n?=?159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ? 5 in total Sharp-van der Heijde Score (?SHS) between inclusion and 1 year (?SHS ?1 or rapid radiographic progression: ?SHS ?5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was independently associated with baseline total SHS (adjusted ??=?0.12; P?=?0.006). It was also associated with ?SHS ?1 (adjusted odds ratio (aOR)?=?1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR?=?1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ?SHS ?5 (aOR?=?2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ?SHS >0 (aOR?=?1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 ?g/ml for ?SHS ?1 and 6.04 ?g/ml for ?SHS ?5, with a good specificity (58% and 75% for ?SHS ?1 and ?SHS ?5, respectively) and high negative predictive values (75% and 92% for ?SHS ?1 or ?SHS ?5, respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.

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Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis.

Publications

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis.

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