scholarly journals Efficacy and Safety of Metformin Use in Rheumatoid Arthritis: A Randomized Controlled Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud Gharib ◽  
Walaa Elbaz ◽  
Ebtissam Darweesh ◽  
Nagwa Ali Sabri ◽  
May Ahmed Shawki

Objective: To evaluate the efficacy and safety of metformin use in rheumatoid arthritis (RA) patients receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs).Methods: A prospective, randomized, controlled, single blinded, study was carried on 66 RA patients with moderate and high disease activity state, receiving csDMARDs. Patients were simply randomized to receive either metformin 850 mg twice daily (Metformin group, n = 33), or placebo twice daily (Control group, n = 33) in addition to their stable anti-rheumatic regimen and followed up for 6 months. Serum C-reactive protein (CRP), disease activity of 28 joints based on CRP (DAS-28-CRP), and quality of life (QOL) were evaluated at baseline and then every 3 months. Moreover, serum adiponectin was assessed at baseline and after 6 months.Results: Sixty patients completed the study. Drop out was due to intolerance to metformin side effects (n = 3) and non-compliance (n = 3). Metformin significantly decreased CRP levels and DAS-28-CRP after 6 months compared to the control group (p-value <0.001). A significant improvement in QOL of metformin group was observed as early as after 3 months (p-value = 0.006) with a continued improvement observed at 6 months (p-value <0.001) compared to the control group. Despite the significantly higher serum adiponectin in the metformin group at baseline, it was significantly reduced after 6 months in the metformin group with median percent change of −63.49% compared to the significant increase in the control group with median percent change of 92.40%.Conclusion: Metformin significantly improved inflammation, disease severity, and QOL in RA patients with high safety profile.Clinical Trial Registration: Clinical-Trials.gov, identifier [NCT08363405].

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 625.2-626
Author(s):  
H. Gerasimova ◽  
T. Popkova ◽  
I. Kirillova ◽  
M. Cherkasova ◽  
A. Martynova ◽  
...  

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment.Objectives:To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period.Methods:The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m.Results:Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28<2,6) was achieved in 54% and 39% pts, low activity levels (DAS28<3,2) – in 46% and 51% pts, respectively.The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL,p<0.05).Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography.There was a good correlation between NT-proBNP level at baseline with age (r=0,55,p<0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23,p=0,01).Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml (p<0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml,p=0,001).After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p<0,05], ΔСRP (R=0,46;p<0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03).In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function.Conclusion:TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts.Disclosure of Interests:None declared


2021 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Khater ES

Aim: to determine ACPA IgG and IL-22 levels in RA patients and their relationship to the disease activity Place and duration of the study: A cross sectional study and prospective cohort study was performed from August 2020 to January 2021 in rheumatology outpatient clinic and laboratory of Al- Quwayiyah General hospital. Methodology: Forty five rheumatoid arthritis patients were included and 35 healthy participants free of any diseases considered as control group. The patients in this study met the American College of Rheumatology's 2010 guidelines. RA Disease activity was assessed for rheumatoid patients using DAS28 scoring. Serum samples collected from the patients and control to perform ESR, Hs-CRP, RF factors and also IL22 and ACPA IgG which were detected using sandwich ELISA and indirect solid phase enzyme immunoassay techniques respectively. Results: Out of the 45 RA patients, 34(75.6%) were females and 11(24.4%) were males aged from (28-67years) with median patient age 42 years. There was no statistically significant difference regarding age and sex between RA patients and control. Thirty (66.7%) of the 45 RA patients had low disease activity or remission, while 15 (33.3%) had moderate to extreme disease activity. Thirty two 32(71.1%) patients of the 45 RA patients had erosive disease. The level of ESR, hs-CRP and RF are increased in the patient group than control, in spite that there were significant differences in the Mean± SD among RA group and control group regarding RF, there was no significant statistical differences ESR, hs-CRP. in the study there was an increase in ACPA and IL-22 levels in patients suffering of RA; 21.52±1.29 U/ml and 71.22±10.63 pg\ml. respectively. While among control there was low serum levels; 14.06±2.01U/ml 33.25±2.41pg\ml and respectively. Significant statistical difference was observed regarding IL-22 and ACPA IgG levels among RA patients and control (P=0.038 and P=0.019 respectively). There is a significant positive relationship (positive correlation) detected between ACPA and IL-22 levels, (r=-0.810; p=0.597). The levels of IL-22 and ACPA were significantly associated with DAS 28. Their relationship was strong as the r value was 0.427 and 0.411 respectively. Conclusion: IL-22 and ACPA IgG levels were highly increased among RA patients in comparison to the control group. The IL-22 and ACPA IgG levels were strongly correlated with the rheumatoid disease activity, DAS 28. These results suggest that Il-22 can be used in association with ACPA IgG level as diagnostic and prognostic markers of rheumatoid arthritis


Author(s):  
Ibrahim A Altamemi ◽  
Sally Alkhafaji

Rheumatoid arthritis is a systemic disease with very complex pathogenesis and feature of chronic synovitis. The biological effect of polymorphism on expression and functionality of IL-23R such as SNP can have functional and phenotypic consequences that make Il-23R as a risk factor for RA disease. Moreover recently there is a new trends to find out a new noninvasive prognostic biomarker for RA disease which may help in fallowing up disease. Thus the aim of present work is to find out if there prognostic value for IL-13 and IL-17in Rheumatoid arthritis through linking its expression level with disease activity score (DAS). Also To study if there is a role for IL-23R 11209026 gene polymorphism in disease susceptibility in Iraqi community by using healthy volunteer as a control group. To achieve this goal a Case control study has been conducted on 40 patient and 40 matched apparently health control. serum IL-17 and IL-13 concentration were measure by enzyme Linked immunosorbent assay According to manufactural instruction,measurement of disease activity was determine according to DAS 28 Score.RFLP PCR was used to study SNP of IL-23R gene polymorphism for patient and control group. Data were summarized, presented and analyzed using statistical package for social science (SPSS version 23). Result of present study found there was significant association between serum IL-17 and IL-13 level and RA disease (P<0, 001; and P<0, 001respectively). Moreover,there is significant positive correlation between expression level of both IL-17 and IL-13 with DAS28 (0.044,and 0.034 respectively). According to Receptor operating Curve both of IL-17 and IL-13 found to have high specificity and sensitivity 100%. Regarding to IL-23 R gene polymorphism,there was no significant correlation between rs11209026 gene polymorphism and susceptibility to rheumatoid arthritis patients in Iraqi community. Thus,present study showed that the concentrations of IL-13 and IL-17 significantly correlated with disease severity and DAS 28 which reflect their prognostic value in RA. Moreover,present study demonstrated that there was no significant association between Il-23R gene rs11209026 polymorphism and susceptibility to RA in Iraqi population.


2018 ◽  
Vol 8 (6) ◽  
pp. 469-474
Author(s):  
G. G. Bagirova ◽  
E. V. Lygina ◽  
S. S. Yakushin ◽  
M. I. Kozminskaya

Objectives:Maximally quickly identify the exacerbation of the disease and timely strengthen the therapy, for more rapid achievement of remission or low disease activity.Methods:The authors created an interactive web portal for self-monitoring of RA activity. The patient management model using this method is that a patient conducts a monthly self-evaluation of the disease activity and transmits this information to his treating doctor in a remote manner via the web portal. In case of worsening and in the absence of any dynamics, according to the patient, he was invited to the center, where this information was verified by a doctor. If, in the patient’s opinion, there was an improvement, he did not come to clinic, but continued therapy. Currently, 30 women with RA, age 57 (38; 71), who completed the 6-month treatment period, are included in the study. 20 women included in the control group, average age 60.5(40; 77).Results:During 6 months, there was a positive dynamic of the course of the disease, the activity of the RA by DAS 28 decreased. Initially, 5 patients (16.7%) had high DAS activity, 24 — moderate (80%), 1low (3.3%). After 6 months of treatment 8 patients (26.7%) had low activity, 22 (73.3%) achieved remission. The mean value of the DAS 28 index at the time of inclusion was 3.99 (2.46; 5.78) and after 6 months of management 2.175 (0.79; 4.31), a statistically significant decrease (Wilcoxon T-test = 5). The DAS 28 index at the time of control group was 4,1 (2.46; 5.78) and after 6 months of management 3,9 (0.79; 4.31), a statistically significant decrease (Wilcoxon T-test = 5). Analysis of clinical and laboratory parameters did not reveal statistically significant deviations.Conclusions:The 6-month period of patient management via the Internet portal for self-monitoring of rheumatoid arthritis activity proved the possibility of achieving remission and low disease activity in all patients.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wendy Walrabenstein ◽  
Marike van der Leeden ◽  
Peter Weijs ◽  
Henriët van Middendorp ◽  
Carlijn Wagenaar ◽  
...  

AbstractLow-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial [RCT] 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score [DAS28] ≤ 5.1, RCT 1, n = 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2, n = 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3, n = 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6–12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1396.2-1397
Author(s):  
H. Sadek ◽  
A. Monir ◽  
S. Bahgat ◽  
M. Elwan ◽  
A. Hamed

Background:Rheumatoid arthritis (RA) is characterized by persistent synovitis that leads to structural joint damage causing deformity and disability. Dickkopf-1(DKK-1) was shown to be a major regulator of joint remodeling, which is associated with subchondral bone erosion in RA. Dickkopf-1 is a secreted glycoprotein that also acts as a potent negative regulator of wingless signaling. Current therapies used to treat RA are not able to effectively repair damaged bone. There is a strong relationship between Wnt signaling pathway, RA and DKK-1 so; this relationship may be a therapeutic point of interestObjectives:To assess the correlation between Dickkopf-1 and RA disease activity, disability, severity and functional status.Methods:Fifty patients fulfilled the 2010 ACR -EULAR criteria for RA were included. Twenty five healthy age and sex matched individuals served as a control (for assessment of serum DKK-1 level). Excluded from the study, patients with Paget disease, Multiple myeloma, Breast cancer, Bone metastasis, Diabetes mellitus, Hyperthyroidism, patients on medication that influence bone metabolism as: heparin, anticonvulsant or thyroxin.All patients were subjected to full history and examination. Disease activity measures as disease activity score (DAS 28-ESR), Visual analogue scale (VAS) and Disease disability indices including ACR criteria of functional status in RA and Health assessment questionnaire disability index (HAQ-DI). Erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), Rheumatoid factor (RF), Anti citrullinated peptide antibody (ACPA) and Serum dickkopf-1 level. Simple erosion narrowing score (SENS) and Ultrasound DAS (US DAS) were done for all patients. Ultrasound DAS included 28 joints, Power Doppler ultrasound (PDUS) examination of 22 joints and gray scale ultrasound (GSUS) examination for Effusion/Hypertrophy (E/H) of 28 joints. Ultrasound erosion count (USEC) and Ultrasound erosion rate (USER) were assessed.Results:Dickkopf-1 level in RA patients ranged from 66 to 453 ng/ml while in the control group ranged from 15 to 87 ng/ml with statistically significant difference. RA patients were grouped in to: group 1 included 15 (30%) patients with normal DKK-1 level and group 2: included 35 (70%) patients with elevated DKK-1. The differences between both groups were highly significant regarding clinical and laboratory measures (duration of morning stiffness, DAS 28, VAS, ESR, CRP, RF and ACPA), and regarding HAQ-DI, SENS and US DAS. We found significant positive correlation between DKK-1 level and laboratory measures (ESR, CRP, RF, ACPA), radiographic parameters (SENS and erosion score), ultrasonographic parameters (US DAS, USEC and USER) and with HAQ-DI and functional status.Conclusion:Serum level of dickkopf-1 was elevated in RA patients and the results demonstrated the relationship between increased dickkopf-1 level and increased disease activity, decreased functional capacity and chronic structural damage suggesting its important role in the pathogenesis of RA.References:[1]Cardona-Rincón A D, Acevedo-Godoy M, Perdomo-Lara S, Chila L, et al. (2018).AB0001 Association of dickkopf1–1 polymorphisms with radiological damage and periodontal disease in patients with early rheumatoid arthritis. Annals of the Rheumatic Diseases; 77(2): 1206.[2]Huang Y, Liu L and Liu A. (2018).Dickkopf-1: Current knowledge and related diseases. Life sciences; 209: 249-54.Disclosure of Interests:None declared


2018 ◽  
Vol 12 (1) ◽  
pp. 189-196
Author(s):  
Noha Abdelsalam ◽  
Ashraf Hussein Mohamed ◽  
Sameh Abdellatif ◽  
Eslam Eid ◽  
Ehsan Mohamed Rizk ◽  
...  

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic & clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P< 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P< 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 & 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.


2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Niaz Albarzinji ◽  
Sherzad Ali Ismael ◽  
Dashty Albustany

Abstract Background Rheumatoid arthritis is a complex multifactorial chronic disease, the importance of human leukocytic antigen (HLA) as a major genetic risk factor for rheumatoid arthritis was studied worldwide. The objective of this study is to identify the association of HLA-DRB1 subtypes with rheumatoid arthritis and its severity in Kurdish region. Methods A case–control study recruited 65 rheumatoid arthritis patients and 100 healthy individuals as control group all over the Kurdistan region/Iraq. Both patient and control groups are genotyped using polymerase chain reaction with sequence specific primer. Anti-CCP antibodies were measured by ELISA test. Rheumatoid factor, C-reactive protein, and disease activity score 28 which measured by DAS-28 values were calculated. The DAS-28 was used to assess the clinical severity of the patients. Results HLA-DRB1-0404 and HLA-DRB1-0405 frequencies showed a strong association with disease susceptibility (P < 0.001). The frequency of HLA-DRB1-0411 and HLA-DRB1-0413 were significantly higher in control group (P < 0.001). The frequency of rheumatoid factor and Anti-CCP were significantly higher among shared epitope-positive patients compared to shared epitope-negative patients (P < 0.001). Regarding the disease activity by DAS-28, rheumatoid arthritis patients didn’t show significant difference between the shared epitope-positive and shared epitope-negative patients. Conclusions HLA-DR0404 and HLA-DR0405 alleles are related to RA, while HLA-DR1-0411 and HLA-DRB1-0413 protect against RA in the Kurdistan region in the North of Iraq.


2020 ◽  
Vol 14 (1) ◽  
pp. 26-36
Author(s):  
William Buwembo ◽  
Ian Guyton Munabi ◽  
Mark Kaddumukasa ◽  
Haruna Kiryowa ◽  
Muhammad Mbabali ◽  
...  

Background . Periodontitis and rheumatoid arthritis have similar epidemiology and pathophysiology. Understanding the interaction between these two diseases is vital in our settings. We set out to assess the effect of oral hygiene interventions on disease activity of rheumatoid arthritis patients with periodontitis in Kampala, Uganda. Methods. Fifty-eight patients attending an arthritis clinic with rheumatoid arthritis and periodontitis were randomly assigned to either an intervention group or a control group. Patients diagnosed with rheumatoid arthritis at least two years before, who were on the same medication, dose, or formulation for RA treatment during the preceding three months, were included. The patients were >18 years of age, would be available for all the study visits in the next six months, had at least six natural teeth, had periodontal disease classified as Dutch Periodontal Index (DPSI) >3 and provided written informed consent. Those who had a chronic disorder requiring chronic or intermittent use of antibiotics, were pregnant, were lactating, or had intent to become pregnant were excluded. The primary outcome measure was a change in Disease Activity Score of 28 Joints (DAS28 score) in two 3-month follow-up periods after the intervention. The secondary outcome measure was a change in periodontal status. Results. There was a statistically significant improvement in the DAS-28 score in both the intervention and control arms during the follow-up period (P<0.01). The participants carrying more than one bacterial species had worse DAS-28 scores. Conclusion. Oral hygiene interventions given to RA patients could drastically improve their RA treatment outcomes, especially in resource-limited settings.


2021 ◽  
Author(s):  
Mustafa Erkut Onder ◽  
Nurdan Orucoglu ◽  
Firat Omar ◽  
Abdullah Canataroglu

Abstract Objective A novel inflammation-based score, C-reactive protein (CRP)-to-albumin ratio (CAR), has been shown to have an association with the inflammatory status in several diseases. We aimed to analyse the association between CAR and disease activity in patients with early rheumatoid arthritis (RA) and to determine the cut-off value of CAR in early and established RA. Methods A total of 177 patients with RA and 111 age and gender-matched healthy controls were included in this study. Cases with a disease duration of less than 1 year were classified as early RA. Serum albumin, CRP, erythrocyte sedimentation rate (ESR), Disease Activity Score-28 (DAS-28-ESR), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were recorded. Results CAR was 2.44 (0.21–30.83) in the RA group and 0.45 (0.21–10.47) in the control group (p<0.001). Eighty-seven (49.15%) of the RA cases were classified as early RA. The analyses indicated that the ESR, CRP and CAR values were higher in patients with early RA than in those with established RA and controls. CAR was correlated with albumin, CRP, ESH, DAS-28 and HAQ scores in both early RA and established RA groups. The receiver operating characteristic curves revealed a CAR cut-off value of 2.67 (80% sensitivity and 85% specificity) and 1.63 (77% sensitivity and 72% specificity) for the prediction of early and established RA, respectively. Conclusion CAR, a formulated ratio, has been described as a predictor for disease activity in patients with early RA as well as in those with established RA. However, CAR has higher sensitivity and specificity for early RA than for established RA.


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