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- Aldridge, Jonathan, et al.
(author)
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Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.
- 2022
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In: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 40:7, s. 1393-1402
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Journal article (peer-reviewed)abstract
- In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
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| 2. |
- Hagel, Sofia, et al.
(author)
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Which patients improve the most after arthritis rehabilitation? A study of predictors in patients with inflamatory arthritis in northern Europe, the STAR-ETIC collaboration
- 2014
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In: Journal of Rehabilitation Medicine. - Uppsala : Foundation of Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 46:3, s. 250-257
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study health-related quality of life (HRQoL) in arthritis rehabilitation performed by multidisciplinary teams in patients with chronic inflammatory arthritis. Predictors of change in health-related quality of life and the proportion of patients with clinical improvement were investigated.DESIGN: Multicentre prospective observational study in 4 European countries.METHODS: HRQoL was measured with the European Quality 5 Dimensions (EQ-5D) and the Short Form 36 Health Survey (SF-36) in 731 patients who underwent multidisciplinary rehabilitation. Potential predictors were physical functioning (Health Assessment Questionnaire (HAQ)), self-efficacy (Arthritis Self Efficacy Scale (ASES)), psychological health (Hopkins Symptom Check List (HSCL-25)), pain/fatigue (numeric rating scales (NRS)), age, sex, diagnosis, comorbidity, education, clinical setting and change of medication during rehabilitation. Analysis of covariance (ANCOVA) was used to assess for potential predictors and interactions. The minimal important differences for HRQoL were analysed.RESULTS: Reporting worse function (b 0.05, p = 0.01), less psychological well-being (b 0.09, p = 0.000), and experiencing more pain (b 0.03, p = 0.000) or fatigue (b 0.02, p = 0.000) at admission predicted improved HRQoL. Change in medication during rehabilitation (b 0.08, p = 0.013) was associated with greater improvement in HRQoL. These EQ-5D findings were supported by SF-36 findings. Positive minimal important differences were noted in 46% (EQ-5D) and 23-47% (SF-36 subscales) of the patients.CONCLUSION: Patients with more severe symptoms experienced the largest gain in HRQoL post-intervention. The results of this study are of value for selecting the right patients for rheumatological team rehabilitation. © 2014 The Authors
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| 3. |
- Hagel, Sofia, et al.
(author)
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Which patients improve the most from arthritis rehabilitation? Results from patients with inflammatory arthritis in northern Europe, the STAR-ETIC collaboration.
- 2014
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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1651-2081 .- 1650-1977. ; 46:3, s. 250-257
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Journal article (peer-reviewed)abstract
- Objective: To study health-related quality of life (HRQoL) in arthritis rehabilitation performed by multidisciplinary teams in patients with chronic inflammatory arthritis. Predictors of change in health-related quality of life and the proportion of patients with clinical improvement were investigated. Design: Multicentre prospective observational study in 4 European countries. Methods: HRQoL was measured with the European Quality 5 Dimensions (EQ-5D) and the Short Form 36 Health Survey (SF-36) in 731 patients who underwent multidisciplinary rehabilitation. Potential predictors were physical functioning (Health Assessment Questionnaire (HAQ)), self-efficacy (Arthritis Self Efficacy Scale (ASES)), psychological health (Hopkins Symptom Check List (HSCL-25)), pain/fatigue (numeric rating scales (NRS)), age, sex, diagnosis, comorbidity, education, clinical setting and change of medication during rehabilitation. Analysis of covariance (ANCOVA) was used to assess for potential predictors and interactions. The minimal important differences for HRQoL were analysed. Results: Reporting worse function (b 0.05, p = 0.01), less psychological well-being (b 0.09, p = 0.000), and experiencing more pain (b 0.03, p = 0.000) or fatigue (b 0.02, p = 0.000) at admission predicted improved HRQoL. Change in medication during rehabilitation (b 0.08, p = 0.013) was associated with greater improvement in HRQoL. These EQ-5D findings were supported by SF-36 findings. Positive minimal important differences were noted in 46% (EQ-5D) and 23-47% (SF-36 subscales) of the patients. Conclusion: Patients with more severe symptoms experienced the largest gain in HRQoL post-intervention. The results of this study are of value for selecting the right patients for rheumatological team rehabilitation.
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| 4. |
- Lend, Kristina, et al.
(author)
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Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis: a post-hoc analysis of a randomized controlled trial (NORD-STAR).
- 2024
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In: Arthritis & rheumatology (Hoboken, N.J.). - 2326-5205. ; 76:3, s. 363-376
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Journal article (peer-reviewed)abstract
- To investigate methotrexate safety and influence of dose on efficacy outcomes in combination with three different biological treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA).This post-hoc analysis included 812 treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial (NCT01491815) to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24weeks of treatment.Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (HR 1.48 [95% CI 1.20 to 1.84]), but not with certolizumab-pegol (HR 0.99 [0.79 to 1.23]) or with abatacept (HR 0.93 [0.75 to 1.16]). With ACT as the reference, methotrexate dose was significantly lower when used in combination with tocilizumab (β -4.65 [95% CI -5.83 to -3.46], p<0.001), with abatacept (β -1.15 [-2.27 to -0.03], p=0.04), and numerically lower in combination with certolizumab-pegol (β -1.07 [-2.21 to 0.07], p=0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations.Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/week, and these were more frequent in combination with tocilizumab versus active conventional treatment. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24weeks.
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| 5. |
- Nielsen, Morten A., et al.
(author)
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Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naïve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts
- 2023
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In: Cells. - : MDPI AG. - 2073-4409. ; 12:2
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Journal article (peer-reviewed)abstract
- Background: Fibroblast-like synoviocytes (FLSs) are essential mediators in the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pauci-immune pathotype respond poorly to currently approved antirheumatic drugs. Galectin-9 (Gal-9) has been reported to directly modulate rheumatoid arthritis (RA) FLSs and to hold both pro- and anti-inflammatory properties. The objective of this study was to evaluate clinical and pathogenic aspects of Gal-9 in RA, combining national patient cohorts and cellular models. Methods: Soluble Gal-9 was measured in plasma from patients with newly diagnosed, treatment-naïve RA (n = 98). The disease activity score 28-joint count C-reactive protein (DAS28CRP) and total Sharp score were used to evaluate the disease course serially over a two-year period. Plasma and synovial fluid samples were examined for soluble Gal-9 in patients with established RA (n = 18). A protein array was established to identify Gal-9 binding partners in the extracellular matrix (ECM). Synovial fluid mononuclear cells (SFMCs), harvested from RA patients, were used to obtain synovial-fluid derived FLSs (SF-FLSs) (n = 7). FLSs from patients suffering from knee Osteoarthritis (OA) were collected from patients when undergoing joint replacement surgery (n = 5). Monocultures of SF-FLSs (n = 6) and autologous co-cultures of SF-FLSs and peripheral blood mononuclear cells (PBMCs) were cultured with and without a neutralizing anti-Gal-9 antibody (n = 7). The mono- and co-cultures were subsequently analyzed by flow cytometry, MTT assay, and ELISA. Results: Patients with early and established RA had persistently increased plasma levels of Gal-9 compared with healthy controls (HC). The plasma levels of Gal-9 were associated with disease activity and remained unaffected when adding a TNF-inhibitor to their standard treatment. Gal-9 levels were elevated in the synovial fluid of established RA patients with advanced disease, compared with corresponding plasma samples. Gal-9 adhered to fibronectin, laminin and thrombospondin, while not to interstitial collagens in the ECM protein array. In vitro, a neutralizing Gal-9 antibody decreased MCP-1 and IL-6 production from both RA FLSs and OA FLSs. In co-cultures of autologous RA FLSs and PBMCs, the neutralization of Gal-9 also decreased MCP-1 and IL-6 production, without affecting the proportion of inflammatory FLSs. Conclusions: In RA, pretreatment plasma Gal-9 levels in early RA were increased and correlated with clinical disease activity. Gal-9 levels remained increased despite a significant reduction in the disease activity score in patients with early RA. The in vitro neutralization of Gal-9 decreased both MCP-1 and IL-6 production in an inflammatory subset of RA FLSs. Collectively these findings indicate that the persistent overexpression of Gal-9 in RA may modulate synovial FLS activities and could be involved in the maintenance of subclinical disease activity in RA.
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