Plasma Metabolome Normalization in Rheumatoid Arthritis Following Initiation of Methotrexate and the Identification of Metabolic Biomarkers of Efficacy

Methotrexate (MTX) efficacy in the treatment of rheumatoid arthritis (RA) is variable and unpredictable, resulting in a need to identify biomarkers to guide drug therapy. This study evaluates changes in the plasma metabolome associated with response to MTX in RA with the goal of understanding the metabolic basis for MTX efficacy towards the identification of potential metabolic biomarkers of MTX response. Plasma samples were collected from healthy control subjects (n = 20), and RA patients initiating MTX therapy (n = 20, 15 mg/week) before and after 16 weeks of treatment. The samples were analyzed by a semi-targeted metabolomic analysis, and then analyzed by univariate and multivariate methods, as well as an enrichment analysis. An MTX response was defined as a clinically significant reduction in the disease activity score in 28 joints (DAS-28) of greater than 1.2; achievement of clinical remission, defined as a DAS-28 < 2.6, was also utilized as an additional measure of response. In this study, RA is associated with an altered plasma metabolome that is normalized following initiation of MTX therapy. Metabolite classes found to be altered in RA and corrected by MTX therapy were diverse and included triglycerides (p = 1.1 × 10−16), fatty acids (p = 8.0 × 10−12), and ceramides (p = 9.8 × 10−13). Stratification based on responses to MTX identified various metabolites differentially impacted in responders and non-responders including glucosylceramides (GlcCer), phosphatidylcholines (PC), sphingomyelins (SM), phosphatidylethanolamines (PE), choline, inosine, hypoxanthine, guanosine, nicotinamide, and itaconic acid (p < 0.05). In conclusion, RA is associated with significant alterations to the plasma metabolome displaying at least partial normalization following 16 weeks of MTX therapy. Changes in multiple metabolites were found to be associated with MTX efficacy, including metabolites involved in fatty acid/lipid, nucleotide, and energy metabolism.

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AB0655 RHEUMATOID ARTHRITIS ACTIVITY BEFORE AND AFTER COVID-19 LOCKDOWN PERIOD

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.576 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1360.1-1360

Author(s):

M. Jordhani ◽

D. Ruci ◽

F. Skana ◽

E. Memlika

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Musculoskeletal Diseases ◽

Statistical Tests ◽

Laboratory Data ◽

World Population ◽

Chronic Patients ◽

Das 28 ◽

Significant Difference ◽

Before And After

Background:The COVID-19 global pandemic has had a great impact on world population due to morbidity, mortality and restriction measures in order to stop the progression of COVID-19.Patients with rheumatic and musculoskeletic diseases, and especially rheumatoid arthritis (RA) patients, being one of the vulnerable classes of chronic patients, were recommended to follow the government’s rules1.Objectives:The aim of this study was to evaluate DAS-28-ESR in patients with rheumatoid arthritis before and after lockdown period.Methods:This is a multi-center observational study including 85 patients which were evaluated before and after lockdown for their disease activity score according to DAS-28-ESR score. They had been diagnosed with rheumatoid arthritis more than 5 years ago. A thorough physical examination was performed before and after the lockdown period. It included examination of tender and swollen joints and patient’s global health. They were completed with all required laboratory data, including erythrosedimentation rate. For a more accurate calculation, DAS-28-ESR was used in an electronic version. Patients with other inflammatory or infective diseases were excluded from the study. All data were statistically evaluated using statistical tests such as t-student test.Results:The first group (the one before lockdown) had an average DAS-28-ESR of 4.7 while after the lockdown period, the average DAS-28-ESR was 5.16.After statistically evaluating all data, it was found that there exists a significant difference between DAS-28-ESR score before and after COVID-19 lockdown (p=0.0011).Conclusion:Our study showed that lockdown period due to COVID-19 pandemic, has aggravated disease activity in patients with Rheumatoid Arthritis. This may be consequence of various causes such as physical inactivity and difficulty to follow-up or to take the medication properly.References:[1]Landewé RB, Machado PM, Kroon F, et al, EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2, Annals of the Rheumatic Diseases 2020;79:851-858.Disclosure of Interests:None declared.

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Metabolomic Profiling Identifies Exogenous and Microbiota-Derived Metabolites as Markers of Methotrexate Efficacy in Juvenile Idiopathic Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.768599 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ryan Sol Funk ◽

Mara L. Becker

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Clinical Response ◽

Enrichment Analysis ◽

P Value ◽

Metabolomic Profiling ◽

Plasma Metabolome ◽

Unsaturated Triglycerides ◽

Metabolic Biomarkers ◽

The Impact

Variability in methotrexate (MTX) efficacy represents a barrier to early and effective disease control in the treatment of juvenile idiopathic arthritis (JIA). This work seeks to understand the impact of MTX on the plasma metabolome and to identify metabolic biomarkers of MTX efficacy in a prospective cohort of children with JIA. Plasma samples from a cohort of children with JIA (n = 30) collected prior to the initiation of MTX and after 3 months of therapy were analyzed using a semi-targeted global metabolomic platform detecting 673 metabolites across a diversity of biochemical classes. Disease activity was measured using the 71-joint count juvenile arthritis disease activity score (JADAS-71) and clinical response to MTX was based on achievement of ACR Pedi 70 response. Metabolomic analysis identified 50 metabolites from diverse biochemical classes that were altered following the initiation of MTX (p < 0.05) with 15 metabolites reaching a false-discovery rate adjusted p-value (q-value) of less than 0.05. Enrichment analysis identified a class-wide reduction in unsaturated triglycerides following initiation of MTX (q = 0.0009). Twelve of the identified metabolites were significantly associated with disease activity by JADAS-71. Reductions in three metabolites were found to be associated with clinical response by ACR Pedi 70 response criteria and represented several microbiota and exogenously derived metabolites including: dehydrocholic acid, biotin, and 4-picoline. These findings support diverse metabolic changes following initiation of MTX in children with JIA and identify metabolites associated with microbial metabolism and exogenous sources associated with MTX efficacy.

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Comparative Analysis of Approaches and Treatment Results of Patients with Early and Nonearly Rheumatoid Arthritis

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.693 ◽

2019 ◽

Vol 7 (17) ◽

pp. 2802-2806

Author(s):

Olga V. Pashanova ◽

Natalia B. Lopatina ◽

Sergey A. Krivosheev ◽

Natalia Y. Baranova

Keyword(s):

Rheumatoid Arthritis ◽

Comparative Analysis ◽

Health Assessment ◽

Laboratory Research ◽

Treatment Results ◽

Hospital Department ◽

Das 28 ◽

Before And After ◽

Associated Conditions ◽

Score Index

The article presents the results of a comparative analysis of different therapy regimens impact on the effectiveness of treatment of patients with early and late rheumatoid arthritis in steady-state. Data on ongoing basis anti-inflammatory therapy of rheumatoid arthritis and the treatment of associated conditions were obtained by continuous copying from case histories of hospital department patients. The observations lasted 12 months. The activity of rheumatoid arthritis before and after the treatment was determined by the DAS 28 (Disease Activity Score) index. The treatment results were evaluated as per the laboratory research and the DAS 28 index, including the counting of painful and swollen joints, erythrocyte sedimentation rate, and health assessment of the patient on a visual analogue scale.

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Changes of DCE‐MRI Parameters in Patients with Rheumatoid Arthritis before and after Therapy and Their Value for the Efficacy Evaluation of Patients

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6848359 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Danguo Chen ◽

Shengquan He

Keyword(s):

Rheumatoid Arthritis ◽

Acute Phase ◽

Chronic Phase ◽

Acute Stage ◽

Time Signal ◽

Efficacy Evaluation ◽

Chronic Stage ◽

Dce Mri ◽

Das 28 ◽

Before And After

Objective. To explore the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in patients with rheumatoid arthritis (RA) before and after therapy and their value for the efficacy evaluation of patients. Methods. Totally, 90 patients with RA confirmed in our hospital between January 2018 and January 2020 were enrolled. All of them were examined with a Siemens Magnetom Avanto 1.5T imaging system, and data about the rate of enhancement in early stage (REE) and steep slope maximum (SSmax) were obtained. Then, the disease activity score in 28 joints (DAS-28), REE, and SSmax were analyzed, and the associations of SSmax and REE with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and DAS-28 were investigated. Additionally, the patients were assigned to the acute-stage group and the chronic-stage group according to their time-signal intensity curves after therapy, and the two groups were compared in SSmax, REE, ESR, CRP, and DAS-28. Corresponding receiver operating characteristic (ROC) curves were drawn for the analysis of potential markers for efficacy improvement in patients. Results. After therapy, REE, SSmax, ESR, DAS-28, and CRP in the synovium of all patients declined greatly (all P < 0.05 ), with higher levels observed in the acute-stage group than those in the chronic-stage group (all P < 0.05 ). SSmax and REE of patients were positively bound up with their ESR, CRP, and DAS-28 (all P < 0.05 ). Additionally, according to ROC curve-based analysis, both SSmax and REE can be adopted as biological indexes for distinguishing between patients at the acute phase from those at the chronic stage, and joint detection of them can boost the sensitivity of DAS-28. Conclusion. The SSmax and REE levels in RA patients after treatment were significantly decreased, and the levels in patients in the chronic phase were lower than those in patients in the acute phase. SSmax and REE are highly expressed in RA patients, and the combined detection can enhance the value of DAS-28 in the assessment of RA, and it is worthy of clinical promotion.

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Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-019-2066-9 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 2

Author(s):

Mikael Brink ◽

Anders Lundquist ◽

Andrey Alexeyenko ◽

Kristina Lejon ◽

Solbritt Rantapää-Dahlqvist

Keyword(s):

Rheumatoid Arthritis ◽

Interferon Alpha ◽

Epithelial Mesenchymal Transition ◽

Enrichment Analysis ◽

Cell Interaction ◽

Protein Profiling ◽

Mesenchymal Transition ◽

Cytokines And Chemokines ◽

Before And After ◽

Alpha Response

Abstract Background Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. Methods A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks. Results There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls. Conclusions We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression.

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Effect of Ramadan fasting on disease activity in patients with rheumatoid arthritis presenting in tertiary care hospital

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.5.2099 ◽

2020 ◽

Vol 36 (5) ◽

Cited By ~ 1

Author(s):

Samara Siddique ◽

M. Yaser Imran ◽

Muhammad Naeem Afzal ◽

Uzma Malik

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Inflammatory Disorder ◽

Care Hospital ◽

Ramadan Fasting ◽

Creative Commons ◽

Das 28 ◽

Before And After

Background and objective: Rheumatoid Arthritis (RA) is a common inflammatory disorder affected by various factors, including fasting. The objective of the study was to establish the effect of Ramadan fasting on DAS 28 in Rheumatoid Arthritis patients. Methods: In this observational cohort study done in department of rheumatology, Mayo hospital, Lahore, between May 2019 to July 2019, 240 patients were divided in fasting (n=120) and non-fasting cohort (n=120) based on their own choice. Mean DAS-28 scores before and after Ramadan was compared in both cohorts with appropriate statistical analyses. Results: Two hundred forty participants, (74 males, 166 females), were recruited. Baseline DAS of fasting group was significantly low (4.35±0.9) as compared to non-fasting group (5.07±0.91). Paired t-test showed statistically significant improvement in fasting and non-fasting groups in total and in both genders (p=0.000). Mean improvement in DAS was numerically greater and statistically significant (p=0.000) in non-fasting group (1.08±0.62) as compared to fasting ones (0.86±0.61). Post-Ramadan DAS was, however, significantly low in fasting group (3.49±0.9) versus non-fasting group (3.98±1.0) (p=0.000). Conclusion: DAS 28 score decreased in both non-fasting as well as fasting patients of RA during the month of Ramadan. RA patients with moderate disease activity, who want to keep fast, can be allowed to do so without any fear of disease worsening. doi: https://doi.org/10.12669/pjms.36.5.2099 How to cite this:Siddique S, Imran Y, Afzal MN, Malik U. Effect of Ramadan fasting on disease activity in patients with rheumatoid arthritis presenting in tertiary care hospital. Pak J Med Sci. 2020;36(5):---------. doi: https://doi.org/10.12669/pjms.36.5.2099 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Role of physiotherapeutic factors in improving peripheral hemodynamics in patients with rheumatoid arthritis

Medical alphabet ◽

10.33667/2078-5631-2019-1-18(393)-44-48 ◽

2019 ◽

Vol 1 (18) ◽

pp. 44-48

Author(s):

G. N. Koshukova

Keyword(s):

Rheumatoid Arthritis ◽

Vascular Complications ◽

Low Frequency ◽

Peripheral Blood Flow ◽

Peripheral Hemodynamics ◽

Blood Filling ◽

Before And After ◽

Duration Of Disease ◽

Vascular Tonus ◽

Clinically Significant

130 rheumatoid arthritiS patients (RA pts) were distributed in the comparative groups on the basis of used physiotherapy methods and placebo‑physiotherapy. Violation of peripheral blood‑flow mainly vessels of small and medium caliber mainly vessels of small and medium caliber in RA pts in comparison with group of practically healthy persons at baseline was detected, the severity of these abnormalities depended on duration of disease. The comparative analysis of basic rheovasographic indexes in RA pts before and after treatment in parallel groups treated with electrosleep‑therapy, low‑frequency magnetotherapy, bioresonant stimulation and placebo‑physiotherapy was conducted. Significant differences in studied indexes after completed course of treatment such as diminishing of asymmetry of blood‑filling in extremities at all types of physiotherapy, increasing of pulse vascular blood‑filling of extremities after electrosleep‑therapy and bioresonant stimulation, decrease of vascular tonus after application of low‑frequency magnetotherapy were defined. Course of placebo‑physiotherapy has not demonstrated statistically meaningful changes in rheovasographic indexes. Clinically significant adverse events during physiotherapy treatment were not detected. Conclusion: including of physiotherapy in the management of RA pts in term to improve peripheral hemodynamics and to prevent vascular complications can be recommended.

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Influence of balneophysical therapy on activity, functional capacity, and quality of life in patients with rheumatoid arthritis

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0904171s ◽

2009 ◽

Vol 137 (3-4) ◽

pp. 171-174 ◽

Cited By ~ 5

Author(s):

Sonja Stojanovic ◽

Aleksandar Dimic ◽

Bojana Stamenkovic ◽

Aleksandra Stankovic ◽

Jovan Nedovic

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

Disease Activity ◽

Functional Capacity ◽

Mean Value ◽

Disease Modifying Antirheumatic Drugs ◽

Das 28 ◽

Before And After ◽

The Mean

Introduction It has been well known that balneophysical therapy has a therapeutic effect on clinical and biological parameters of disease activity in the patients with rheumatoid arthritis (RA). Objective. To determine the influence of balneophysical therapy on functional capacity, activity and quality of life of the patients with RA primarily treated with some of disease modifying antirheumatic drugs. Methods. The study enrolled 73 patients with RA treated with some of disease modifying antirheumatic drugs (Methotrexate in 85% of patients). During hospitalization at the Clinical Rheumatologic Department of the Institute 'Niska Banja', the patients were treated, beside the medicamentous therapy, by hydrotherapy (oligomineral, homeothermic, low radioactive water), mineral peloid therapy, electrotherapy and kinesiotherapy. Before and after balneotherapy, the patients filled in the Health Assessment Questionnaire (HAQ) and the Quality of Life Rheumatoid Arthritis (QOL-RA) scale. The Disease Activity Score (DAS) 28 was used to measure the disease activity before and after balneotherapy. A possible value of HAQ was from 0 to 3, and QOL-RA from 0 to 10. Results. The mean value of the duration of balneophysical therapy was 14.7?4.8 days. We found significant improvement of functional capacity in the patients with RA. The average HAQ score before balneotherapy was 1.07?0.61, and 0.86?0.55 after balneotherapy, which was statistically significantly lower (p<0.05). DAS 28 after balneotherapy was also statistically significantly lower than DAS 28 before balneotherapy: the mean value of DAS 28 before therapy was 6.30?0.81 and after therapy 5.48?0.75 (p<0.001). The quality of life significantly improved after balneophysical therapy: the mean value of QOL-RA scale before therapy was 5.38?1.62 and after therapy 7.35?1.81 (p<0.05). Conclusion. Balneophysical therapy, when properly dosed, is an effective, adjuvant therapy in the patients with RA of mild disease activity. Balneophysical therapy has a positive influence on disease activity, functional capacity and quality of life in the patients with rheumatoid arthritis.

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EVALUATION OF THE EFECTS OF ELECTRONIC ACUPUNCTURE COMBINED WITH “TAM TY THANG” REMEDY IN THE TREATMENT OF RHEUMATOID ARTHRITIS BY WIND-COLD-DAMP

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2016.6.17 ◽

2017 ◽

pp. 122-127

Author(s):

Thi Luu Nguyen ◽

Thi Tan Nguyen

Keyword(s):

Rheumatoid Arthritis ◽

Side Effects ◽

Prospective Study ◽

Key Words Rheumatoid Arthritis ◽

Good Effect ◽

Good Level ◽

Relieve Pain ◽

Level Of Activity ◽

Before And After ◽

The Moment

Objectives: To assess the effect of electronic acupuncture combined with “Tam ty thang” remedy in the treatment of rheumatoid arthritis by wind-cold-damp. Materials and methods: prospective study, comparing before and after treatment, including 43 patients who were diagnosed with rheumatoid arthritis by wind-cold-damp according to traditional medicine. Results: good level occupied 69,8%, and fair good level occupied 30,2%.The improved motor function accounted for 95.3%, to relieve pain up to 95,3%, reducing inflammation of VSS in 1 hour at the moment No 31,65, N28 17,88. The improvement in the level of activity of the hand reached 48,8% for good level. Conclusions: The method of electronic acupuncture combined with “Tam ty thang” remedy have a good effect in the treatment of rheumatoid arthritis by wind-cold-damp and it didn’t cause significantly side effects in clinic. Key words: rheumatoid arthritis, electronic acupuncture, “Tam ty thang” remedy

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Body Mass Index Impact on Disease Activity, Clinical and Sonographic Remission Rates in Patients with Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573397115666181130143239 ◽

2019 ◽

Vol 15 (3) ◽

pp. 215-223

Author(s):

Tanya Sapundzhieva ◽

Rositsa Karalilova ◽

Anastas Batalov

Keyword(s):

Rheumatoid Arthritis ◽

Body Mass Index ◽

Disease Activity ◽

Body Mass ◽

Normal Weight ◽

Clinical Disease ◽

Clinical Disease Activity ◽

Das 28 ◽

Remission Rates ◽

Activity Indices

Aim: To investigate the impact of body mass index (BMI) on clinical disease activity indices and clinical and sonographic remission rates in patients with rheumatoid arthritis (RA). Patients and Methods: Sixty-three patients with RA were categorized according to BMI score into three groups: normal (BMI<25), overweight (BMI 25-30) and obese (BMI≥30). Thirty-three of them were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and 30 with biologic DMARDs (bDMARDs). Patients underwent clinical and laboratory assessment and musculoskeletal ultrasound examination (MSUS) at baseline and at 6 months after initiation of therapy. We evaluated the rate of clinical and sonographic remission (defined as Power Doppler score (PD) = 0) and its correlation with BMI score. Results: In the csDMARDs group, 60% of the normal weight patients reached DAS28 remission; 33.3% of the overweight; and 0% of the obese patients. In the bDMARDs group, the percentage of remission was as follows: 60% in the normal weight subgroup, 33.3% in the overweight; and 15.8% in the obese. Within the csDMARDs treatment group, two significant correlations were found: BMI score–DAS 28 at 6th month, rs = .372, p = .033; BMI score–DAS 28 categories, rs = .447, p = .014. Within the bDMARDs group, three significant correlations were identified: BMI score–PDUS at sixth month, rs = .506, p =.004; BMI score–DAS 28, rs = .511, p = .004; BMI score–DAS 28 categories, rs = .592, p = .001. Sonographic remission rates at 6 months were significantly higher in the normal BMI category in both treatment groups. Conclusion: BMI influences the treatment response, clinical disease activity indices and the rates of clinical and sonographic remission in patients with RA. Obesity and overweight are associated with lower remission rates regardless of the type of treatment.

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