scholarly journals Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Iván Arias de la Rosa ◽  
Alejandro Escudero-Contreras ◽  
Miriam Ruiz-Ponce ◽  
Cristóbal Román-Rodríguez ◽  
Carlos Pérez-Sánchez ◽  
...  

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

2020 ◽  
Vol 49 (1) ◽  
pp. 20190186
Author(s):  
Mostafa Mahmoud Youssef Mohamed ◽  
Mushira M. Dahaba ◽  
Mary Medhat Farid ◽  
Adel Mahmoud Ali Elsayed

Objectives: This study was undertaken as an attempt to assess radiographic temporomandibular joint (TMJ) changes in relation to rheumatoid factor (RF), anticitrullinated protein (ACCP) antibodies and disease activity score 28 (DAS28) in rheumatoid arthritis (RA) patients to find the best predictor of rheumatoid affection of the TMJ with the ultimate goal of maintaining TMJ function and preventing joint damage. Methods: 20 Rheumatoid Arthritis patients as well as 20 volunteers were included in this study. RA group were assessed for RF, ACCP, DAS28. Both groups were assessed by CBCT for TMJ dimensions and radiographic osteoarthritic changes. All data were statistically analyzed. Results: Rheumatoid Arthritis group showed significantly less condylar height and more radiographic osteoarthritic changes than the control group. RF showed no significant correlation with either TMJ measurements or TMJ radiographic osteoarthritic changes. ACCP showed significant inverse correlation with condylar height and anteroposterior (AP) dimensions, but non-significant relation with mediolateral dimension and radiographic osteoarthritic changes. DAS28 showed significant inverse correlation with condylar AP and mediolateral dimensions. It also showed significant correlation with flattening of the TMJ condylar head and flattening of the articular fossa. Patients with high and moderate disease activity showed significantly smaller AP TMJ dimension than patients with low disease activity. Disease activity showed statistically significant direct correlation with all osteoarthritic changes except for erosions of the glenoid fossa and condyle. Conclusion: Disease Activity Score28 score and disease activity are strong indicators of TMJ affection in RA patients when compared to RF and ACCP. ACCP is a better indicator of changes in condylar measurements than TMJ osteoarthritic changes. While RF is the least efficient indicator of TMJ involvement in RA patients.


2019 ◽  
Vol 78 (12) ◽  
pp. 1609-1615 ◽  
Author(s):  
Daniel Aletaha ◽  
Jen-fue Maa ◽  
Su Chen ◽  
Sung-Hwan Park ◽  
Dave Nicholls ◽  
...  

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses.ResultsIn the larger study (N=207), a greater number of prior DMARDs (>2 vs 0–1) was associated with smaller improvements in DAS28(CRP) (–1.8 vs –2.2), SDAI (–22.1 vs –26.9) and HAQ-DI (–0.43 vs –0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings.ConclusionsNumber of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.


2020 ◽  
pp. 87-95
Author(s):  
Alice Mason ◽  
Mariam Malik

In recent years, a new concept of prehabilitation, enhancing an individual’s functional capacity ahead of a medical intervention, has begun to be explored in the fields of surgery and oncology, with positive results. This article explores applying the principle of prehabilitation to patients with rheumatoid arthritis prior to starting advanced therapies, including biologic disease-modifying antirheumatic drugs and targeted synthetic disease-modifying antirheumatic drugs. In this article, the literature is reviewed and the existing evidence is summarised, and the suggestion is that this approach could improve a patient’s chance of achieving low disease activity or remission. There are a number of opportunities for improving the likelihood of patients with rheumatoid arthritis having a good response to therapy. Research shows that smokers starting TNF inhibitors are less likely to achieve a good response compared to non-smokers. Obese patients are also less likely to achieve a good response with TNF inhibitors; female patients with obesity may be less likely to achieve a good response with tocilizumab and early real-world data suggest there may be a reduced response to JAK inhibitors. Rheumatoid arthritis patients experiencing depression are less likely to respond to TNF inhibitors. Increased physical activity is potentially beneficial for all rheumatoid arthritis patients, although the effect on response to specific drugs has been less widely explored. Prehabilitation approaches could include targeting smoking cessation, improving physical activity, providing psychological support, optimising BMI, and dietary changes. A number of studies have shown that each of these interventions can lead to significant improvements in disease activity scores, with some patients potentially benefitting from more than one intervention. The authors identify principles for delivering prehabilitation in practice and suggest that this is an exciting area for ongoing research.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Benucci ◽  
Gianantonio Saviola ◽  
Mariangela Manfredi ◽  
Piercarlo Sarzi-Puttini ◽  
Fabiola Atzeni

The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.


Author(s):  
Sahar A. Ahmed ◽  
Enas M. Darwish ◽  
Walaa A. Attya ◽  
Mai Samir ◽  
Mennatallah Elsayed ◽  
...  

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.


Author(s):  
Małgorzata Łączna ◽  
Damian Malinowski ◽  
Agnieszka Paradowska-Gorycka ◽  
Krzysztof Safranow ◽  
Violetta Dziedziejko ◽  
...  

Abstract Aim Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. Methods The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. Results After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test. Conclusions The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1099.1-1099
Author(s):  
F. Pistillo ◽  
A. La Rosa ◽  
P. De Sandre ◽  
E. Fracassi ◽  
G. Scanelli ◽  
...  

Background:Many patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are in their childbearing years. Concerns exist regarding the interplay between the rheumatic diseases and the pregnancy (1).Objectives:Actually, there are contradictory data regarding the pregnancy outcome in patients with RA and SpA (2). Thus, we performed this longitudinal retrospective study to evaluate the effect of RA and SpA on pregnancy outcome.Methods:The data of 78 pregnancies of 60 women followed from April 2017 to December 2020 at pregnancy clinic of Internal Medicine Unit, San Bortolo Hospital, Vicenza and Rheumatology Unit, University of Verona were reviewed. Fifty (64.1%) women were affected by RA and 28 (35.9%) by SpA. Information regarding demographic data, disease activity, drug exposure and maternal/foetal outcomes were collected in an electronic database. Details concerning pregnancy complications and congenital malformation were also collected. We compared pregnancy and foetal/neonatal outcome, medication use and disease activity between women affected by RA and SpA. Moreover, we evaluated the effect of disease activity on pregnancy outcome.Results:Overall, there were 70 (86.4%) live births, 10 (12.3%) miscarriages and 1 (1.2%) foetal death. There were three twin pregnancies. Even there was a higher rate of glucocorticoids and bDMARDs use in RA than in SpA group, respectively 40% vs 21% and 70% vs 57,1%, there were no statistical differences regarding drug exposure at conception. Moreover, there were no differences concerning disease activity at conception. Still, a higher rate of glucocorticoids and bDMARDs, respectively 26% vs 10.7% and 46% vs 39.3% were used in RA than in SpA patients during pregnancy. Furthermore, we did not find any statistical differences regarding maternal and foetal/neonatal outcome between pregnancies in the RA and those in the SpA groups. There were four (4.9%), congenital malformation, two (3.8%) in RA group and two (6.9%) in SpA group. About one-third of patients 24 (30.7%) presented a moderate disease activity at conception as evaluated by DAS28PCR and BASDAI. However, there were no significant differences, on maternal and foetal/neonatal outcome in patients with moderate activity disease with respect of those in clinical remission.Conclusion:Even a higher rate of glucocorticoids and bDMARDs were used in RA than in SpA patients, there was no differences on pregnancy outcome between them.References:[1]Ostensen M. Nat Rev Rheumatol. 2017;13:485-493. doi: 10.1038/nrrheum.2017.102.[2]Polachek et al. J Rheumatol 2020;47:161-163. doi: 10.3899/jrheum.190631.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 929.1-930
Author(s):  
Y. M. Pers ◽  
V. Valsecchi ◽  
T. Mura ◽  
S. Aouinti ◽  
N. Filippi ◽  
...  

Background:Telemedicine has found wider application in chronic diseases for encouraging tight home-monitoring in order to improve patients’ outcome (Smolen et al. 2017).In previous studies, a high feasibility and high patient-satisfaction rate was found as well as the evidence for a superior or equal effectiveness of telemedicine compared to the standard face-to-face approach, however the results were weakened by some methodological biases and wide heterogeneity of interventions, thus preventing to draw definitive conclusions (Piga et al. 2017; Najm, Gossec, et al. 2019).Objectives:In rheumatoid arthritis (RA), telemedicine may allow a tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician’s interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA.Methods:A 6-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new Disease Modifying Anti-Rheumatic Drug (DMARD) therapy. Two groups were established: “connected monitoring” and “conventional monitoring”. The primary outcome was the number of physical visits between baseline and 6 months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional, and health status scores (SF-12).Results:Of the 94 randomized patients, 89 completed study: 44 in the “conventional monitoring” arm and 45 in the “connected monitoring” arm. The total number of physical visits between baseline and 6 month was significantly lower in the “connected monitoring” group (0.42 ± 0.58 versus 1.93 ± 0.55; p<0.05). No differences between groups were observed in the clinical and functional scores. A better quality of life for SF-12 subscores (Role-Physical, Social-Functioning and Role-Emotional) were found in the “connected monitoring” group.Conclusion:According to our results, a connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment.References:[1] Najm, Aurelie, Laure Gossec, Catherine Weill, David Benoist, Francis Berenbaum, and Elena Nikiphorou. 2019. “Mobile Health Apps for Self-Management of Rheumatic and Musculoskeletal Diseases: Systematic Literature Review.”JMIR MHealth and UHealth7 (11): e14730.https://doi.org/10.2196/14730.[2] Piga, Matteo, Ignazio Cangemi, Alessandro Mathieu, and Alberto Cauli. 2017. “Telemedicine for Patients with Rheumatic Diseases: Systematic Review and Proposal for Research Agenda.”Seminars in Arthritis and Rheumatism47 (1): 121–28.https://doi.org/10.1016/j.semarthrit.2017.03.014.[3] Smolen, Josef S, Robert Landewe, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, et al. 2017. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2016 Update.”Annals of the Rheumatic Diseases76 (6): 960–77.https://doi.org/10.1136/annrheumdis-2016-210715.Disclosure of Interests:None declared


2014 ◽  
Vol 61 (1-2) ◽  
pp. 24-30 ◽  
Author(s):  
Alvin Yee ◽  
Tyler Webb ◽  
Andrea Seaman ◽  
Maria Infantino ◽  
Francesca Meacci ◽  
...  

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