scholarly journals Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 241 ◽  
Author(s):  
Rónán Daly ◽  
Gavin Blackburn ◽  
Cameron Best ◽  
Carl S. Goodyear ◽  
Manikhandan Mudaliar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clear Correlation ◽  
Strategy Study ◽  
Reactive Protein ◽  
Score Following ◽  
Activity Assessment ◽  
Ultrasound Assessment ◽  
First Time ◽  
Rheumatic Drug

Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway.

scholarly journals Plasma Itaconate elevation following successful cDMARD treatment in early rheumatoid arthritis patients elucidates disease activity associated macrophage activation

2019 ◽  
Author(s):  
Rónán Daly ◽  
Gavin Blackburn ◽  
Manikhandan Mudaliar ◽  
Karl Burgess ◽  
Anne Stirling ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Macrophage Activation ◽  
Response To Treatment ◽  
Clear Correlation ◽  
Newly Diagnosed ◽  
Strategy Study ◽  
Ultrasound Assessment ◽  
Pathway Analyses

AbstractObjectiveTo characterize changes in the plasma metabolic profile in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease modifying anti-rheumatic drug (cDMARD) therapy.MethodsPlasma samples collected in an early RA randomized strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and 3 months post commencement of non-biologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the 3 month timepoint.ResultsA total of ten metabolites exhibited a clear correlation with reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate coA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of CRP.ConclusioncDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of an inflammatory disease in humans. Quantitative metabolic biomarker based tests of clinical change in state are feasible and should be developed around the itaconate pathway.Key MessagesWhat is already known about this subject?Rheumatoid arthritis is associated with perturbations in metabolic activity, which have also been associated with response to certain treatments. In vitro work on immunometabolism has recently revealed itaconate as a key metabolite controlling macrophage activation.What does this study add?In newly diagnosed RA, commencement of csDMARD therapy is associated with changes in the levels of ten metabolites (especially itaconate and its derivatives) that correlate to a corresponding fall in disease activity Pathway analyses suggest these metabolites are associated with macrophage activation.How might this impact on clinical practice?Changes in metabolite levels in response to treatment provide additional new insights into RA pathogenesis that suggest a focus on macrophage activation state. The association of increased itaconate with decreased inflammation point to possible routes of intervention in RA.

scholarly journals Prognosis of pneumonia in patients with rheumatoid arthritis: the role of medication and disease activity prior to admission a population-based cohort study

RMD Open ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e001102 ◽  
Author(s):  
Mette Holland-Fischer ◽  
Reimar W Thomsen ◽  
Ulrik Tarp ◽  
Mette Nørgaard
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Disease Activity ◽  
Population Based ◽  
C Reactive Protein ◽  
Subsequent Infection ◽  
Reactive Protein ◽  
Increased Risk ◽  
First Time

ObjectivePatients with rheumatoid arthritis (RA) experience an increased risk of infections, but the prognosis of infections is unclear. We examined if patients with RA have worse outcomes from pneumonia than non-RA individuals.MethodsIn a population-based cohort study, we computed 90-day mortality rates and crude and adjusted HRs comparing pneumonia patients with and without RA. Among patients with RA, we evaluated prognostic effects of RA medications including prednisolone and disease activity as assessed by C reactive protein (CRP) or platelet levels measured 30–180 days before admission to avoid any influence from the subsequent infection.ResultsAmong 52 577 patients hospitalised for the first time with pneumonia, 1220 (2.3%) had RA. The 90-day mortality was 19.9% for patients with RA and 18.9% for non-RA patients (adjusted 90-day HR of 1.05 (95% CI 0.92 to 1.19)). Compared with CRP levels <8 mg/L, CRP levels ≥20 mg/L predicted increased mortality in patients with RA with adjusted 90-day HRs of 4.98 (95% CI 2.19 to 11.36). Compared with methotrexate monotherapy, both prednisolone (HR 1.43 (95% CI 0.91 to 2.22)) and no RA therapy (HR 1.35 (95% CI 0.85 to 2.14)) tended to increase 90-day mortality. Compared with patients who used prednisolone and had low CRP levels, high CRP predicted increased mortality both in patients who used prednisolone (HR 3.09, 95% CI 1.25 to 7.65) and those who did not (HR 2.35, 95% CI 0.94 to 5.87).ConclusionsOverall, RA does not increase mortality following hospitalisation for pneumonia. However, high RA disease activity prior to admission predicts increased pneumonia mortality in patients regardless of prednisolone use.

scholarly journals Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

FRI0126 POOR ADHERENCE TO METHOTREXATE IS ASSOCIATED WITH PERSISTENT DISEASE ACTIVITY DURING FOLLOW-UP FOR RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 644.1-645
Author(s):  
J. H. Kang ◽  
S. E. Choi ◽  
H. Xu ◽  
D. J. Park ◽  
S. S. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Outcome ◽  
Disease Activity ◽  
Reactive Protein ◽  
Rate Score ◽  
Tertiary Center ◽  
Proportion Of Days Covered ◽  
Euroqol 5D ◽  
Control Disease

Objectives:Although methotrexate (MTX) is the cornerstone therapy in patients with rheumatoid arthritis (RA), adherence to MTX in these patients is typically suboptimal. Thus, we investigated the proportion of RA patients who were adherent to MTX and whether non-adherence to MTX affected the clinical outcome in these patients during follow-up.Methods:We enrolled 331 RA patients from a single tertiary center. Data were collected at the time of enrollment and then annually for 4 consecutive years. Adherence was defined by the proportion of days covered at 1 year. Patients were divided into two groups: patients who took more than 80% of MTX and those who did not. Univariate and multivariate analyses were performed to identify the association between drug compliance and clinical outcome.Results:Of the 331 RA patients, 8.7% had taken less than 80% of MTX during the follow-up period. Non-adherent patients had lower EuroQol-5D scores (P=0.013) and higher RAPID3 scores (P=0.004) at baseline than adherent patients. Leflunomide was more commonly prescribed to adherent patients than non-adherent patients (P=0.012). Non-adherent patients had a higher mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate score (P=0.001), higher mean DAS28-C-reactive protein (CRP) score (P=0.001), and higher mean rate of tender and swollen joints (P=0.003 and P=0.002, respectively) than adherent patients. In the multivariate analysis, poor MTX adherence was significantly associated with a higher mean DAS28-CRP score (odds ratio, 0.270; 95% confidence interval, 0.165–0.444; P<0.001).Conclusion:Adherence to MTX can affect disease activity during follow-up in Korean patients with RA. Our results provide a rationale for patient education to maintain good drug adherence in RA patients, to control disease activity.Disclosure of Interests:None declared

scholarly journals Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Kurz ◽  
Manfred Herold ◽  
Elisabeth Russe ◽  
Werner Klotz ◽  
Guenter Weiss ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Systemic Autoimmune Disease ◽  
Das28 Score ◽  
Reactive Protein ◽  
Adalimumab Therapy ◽  
Receptor Activator ◽  
Joint Erosions ◽  
Factor Therapy ◽  
Necrosis Factor

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.

scholarly journals The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

2021 ◽  
Author(s):  
Yongji Li ◽  
Wendi Yang ◽  
Feng Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Treatment Efficacy ◽  
Th17 Cells ◽  
Immune Cell ◽  
Disease Risk ◽  
Th1 Cells ◽  
Clinical Role ◽  
Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

Disease activity assessment in rheumatoid arthritis

2020 ◽  
pp. 161-168
Author(s):  
Josef Smolen
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Pain ◽  
Joint Stiffness ◽  
Treat To Target ◽  
Therapeutic Decision ◽  
Activity Assessment ◽  
Disease Modifying ◽  
Therapeutic Decision Making ◽  
Disease Activity Assessment

The major clinical hallmarks of rheumatoid arthritis (RA) are articular swelling, joint pain, and morning joint stiffness. Disease activity assessment is pivotal when following patients with RA throughout the course of their disease, and especially when assessing improvement or deterioration upon institution of the necessary therapies. To prevent an adverse outcome, it is essential to diagnose the disease early and to start treatment with disease-modifying antirheumatic drugs (DMARDs) immediately after diagnosis. Adhering to the treat-to-target approach, which is a central strategy irrespective of the type of treatment available and the therapy applied, requires consistency in using validated composite measures of disease activity. Rather than a mere matter of using specific therapies, it is also a matter of using tools for disease activity assessment to guide therapeutic decision-making. This enables offering and achieving the best possible outcomes for RA patients.

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