scholarly journals Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 880 ◽  
Author(s):  
Yen-Ju Lin ◽  
Martina Anzaghe ◽  
Stefan Schülke
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Bone Erosion ◽  
Treatment Options ◽  
Joint Damage ◽  
Cartilage Destruction ◽  
Biologic Dmards ◽  
Clinical Benefits ◽  
Synthetic Dmards ◽  
Inability To Work

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

scholarly journals Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

2021 ◽  
Author(s):  
dima abdelhafiz ◽  
Tara Baker ◽  
Alice galscow
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Disease Activity ◽  
Bone Erosion ◽  
English Literature ◽  
Joint Damage ◽  
Cartilage Destruction ◽  
Diagnosis And Treatment ◽  
Pre Treatment ◽  
One Year

Background Rheumatoid Arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. Aim To systematically explore the role of the biomarkers: C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. Methods A systematic review of the English literature using four different databases was carried out. Results CRP>7.1 mg/L predicted poor conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity, but was associated with increased radiographic damage (r=0.46, p=0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. 14-3-3η significantly correlated with inflammation, bone remodelling and osteoporosis in RA patients (p<0.05). 14 3 3η positively correlated with RA duration (p=0.003), disease activity and positive RF (P=0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity, after 6 and 12 weeks of treatment (p<0.05). MBDA score was able to differentiate between small differences in disease activity and predicted remission over one year period. Conclusion The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area.

scholarly journals The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Targets ◽  
Triple Helix ◽  
Cancer Metastasis ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Patient Treatment ◽  
Collagen Triple Helix ◽  
Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

scholarly journals Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000898 ◽  
Author(s):  
Desirée van der Heijde ◽  
Michael Schiff ◽  
Yoshiya Tanaka ◽  
Li Xie ◽  
Gabriella Meszaros ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Phase Iii ◽  
Inadequate Response ◽  
Smallest Detectable Change ◽  
Structural Joint ◽  
Synthetic Dmards ◽  
Modified Total Sharp Score

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR).MethodsPatients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data.ResultsOf 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01).ConclusionsTreatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

scholarly journals The Relationship Between Synovial Pathobiology and Magnetic Resonance Imaging Abnormalities in Rheumatoid Arthritis: A Systematic Review

2017 ◽  
Vol 44 (9) ◽  
pp. 1311-1324 ◽  
Author(s):  
Frances Humby ◽  
Arti Mahto ◽  
Muaaze Ahmed ◽  
Andrew Barr ◽  
Stephen Kelly ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Magnetic Resonance Imaging ◽  
Systematic Review ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Bone Erosion ◽  
Critical Role ◽  
Joint Damage ◽  
Resonance Imaging ◽  
The Relationship

Objective.Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to reliably identify synovitis, bone marrow edema, bone erosion, and joint space narrowing (JSN)/cartilage loss. Understanding the exact relationship between each MRI feature and local synovial pathobiology is critical to dissect disease pathogenesis as well as develop future predictive models.Methods.A systematic review was performed of the current published literature examining the relationship between MRI abnormalities and synovial pathobiology in patients with RA.Results.Eighteen studies were identified; most focused on validation of MRI as a tool to detect and quantify synovitis, with a significant relationship demonstrated. Additionally, from the limited data available, a critical role seems likely for synovial pathways, at least in driving joint damage. However, there was a lack of data examining the relationship between synovial pathobiology and bone marrow abnormalities and JSN.Conclusion.Although understanding the interrelationship of these disease biomarkers offers the potential to enhance the predictive validity of modern imaging with concomitant synovial pathobiological analysis, further studies integrating MRI with synovial tissue analysis in well-controlled cohorts at distinct disease stages before and after therapeutic intervention are required to achieve this.

scholarly journals Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Jiah Yeom ◽  
Dong Joon Yim ◽  
Seongho Ma ◽  
Young-Hee Lim
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Bone Destruction ◽  
In Vivo Studies ◽  
Propionibacterium Freudenreichii ◽  
Limited Information ◽  
Collagen Induced Arthritis

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

scholarly journals Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Qinghua Fang ◽  
Chun Zhou ◽  
Kutty Selva Nandakumar
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Joint Damage ◽  
Factors Affecting ◽  
Clinical Onset ◽  
Autoimmune Syndrome ◽  
Immune Balance ◽  
Comprehensive Knowledge ◽  
Bone Damage ◽  
Cellular Pathways

Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development. During this process, several signaling molecules (RANKL-RANK, NF-κB, MAPK, NFATc1, and Src kinase) are activated in the osteoclasts, cells responsible for bone resorption. Hence, comprehensive knowledge on pathogenesis is a prerequisite for prevention and development of targeted clinical treatment for RA patients that can restore the immune balance improving clinical therapy.

Rheumatoid arthritis

2020 ◽  
pp. 4415-4440
Author(s):  
Kenneth F. Baker ◽  
John D. Isaacs
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Inflammation ◽  
Kinase Inhibitors ◽  
Joint Damage ◽  
Premature Mortality ◽  
Treat To Target ◽  
Optimal Care ◽  
Acute Phase Reactants ◽  
Disease Remission ◽  
Synthetic Dmards

Rheumatoid arthritis is a common autoimmune disease characterized by both synovial and systemic inflammation. Synovitis classically presents as a symmetrical destructive polyarthritis affecting the hands and feet typified by episodic pain, stiffness, and swelling. Systemic inflammation leads to a range of extra-articular manifestations including organ involvement (e.g. interstitial lung disease, scleritis), constitutional features (e.g. fatigue, depression) and other complications (e.g. accelerated atherosclerosis, nerve and spinal cord compression). Rheumatoid arthritis is a clinical diagnosis based largely upon history and examination, supported by a limited range of investigation findings including elevated acute-phase reactants, autoantibodies (rheumatoid factor and anti-citrullinated peptide antibody), and imaging (e.g. musculoskeletal ultrasound). If left untreated, patients can rapidly develop irreversible joint damage leading to chronic pain, deformity, disability, and premature mortality. However, with early initiation of disease-modifying anti-rheumatic drugs (DMARDs) in treat-to-target strategies, disease remission is now achievable for many patients. Conventional synthetic DMARDs are the anchor of rheumatoid arthritis therapy, with methotrexate the recommended first choice. Biological DMARDs (monoclonal antibodies and soluble receptors) and targeted synthetic DMARDs (Janus kinase inhibitors) are reserved as second-line agents. Glucocorticoids are helpful as bridging therapy, though their considerable side effect profile prohibits their use as maintenance therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in relieving arthritis pain, but long-term use is limited by their potential cardiovascular, renal, and gastrointestinal toxicities. With optimal care from a multidisciplinary team, many patients achieve and retain disease remission with maintenance of employment and quality of life.

scholarly journals SAT0057 PREDICTING INADEQUATE RESPONSE TO JAK INHIBITORS BY CLUSTER ANALYSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 960.1-961
Author(s):  
M. Sugawara ◽  
Y. Fujieda ◽  
A. Noguchi ◽  
S. Tanimura ◽  
Y. Shimizu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cluster Analysis ◽  
Bone Erosion ◽  
Japanese Patients ◽  
User Group ◽  
Biologic Dmards ◽  
Chugai Pharmaceutical ◽  
Significant Difference ◽  
History Of ◽  
Group B

Background:Oral Janus kinase inhibitors (JAKi) have dramatically altered outcomes in patients with rheumatoid arthritis (RA). However, there remains some proportion of patients who respond to inadequately JAKi treatment (JAKi-IR) [1,2]. The characteristics in RA patients associated with JAKi-IR have not been fully demonstrated.Objectives:To clarify the characteristics of JAKi-IR in patients with RA by cluster analysis.Methods:This retrospective study comprised 120 RA patients who were treated with JAKi (Tofacitinib or Baricitinib) between July 2013 and September 2019 in five facilities. The disease status at the baseline, at 12 weeks after JAKi treatment and at the time point of withdrawing JAKi was assessed using the Disease Activity Score (DAS28) and the American College of Rheumatology (ACR) response criteria. JAKi-IR was defined as follows, primary non-response at 12 weeks after JAKi treatment: withdrawal of JAKi with ACR20 non-response or non-improvement in DAS28-CRP (ΔDAS28-CRP<1.2 from baseline), secondary non-response: withdrawal of JAKi without clinical remission after 12 weeks. Hierarchical cluster analysis was performed with the following variables: gender, age, disease duration, bone erosion, ACR functional classification (Class ≥3), comcomitant rheumatoid arthritis related interstitial lung disease (RA-ILD) or other autoimmune disease (AID), anti-citrullinated protein antibody (ACPA) positivity, rheumatoid factor (RF) at baseline, use/dose of methotrexate (MTX) and prednisolone (PSL), serum ESR/CRP, tender/swollen joint counts (TJC/SJC), visual analog scale by patients (VAS-Pt), and prior of biologic DMARDs.Results:The 120 enrolled patients were classified into 4 groups by cluster analysis(Figure1), The characteristics of each group are as follows, Group A(n=21): female + bone erosion + RF/ACPA positive + AID + MTX non-user, Group B(n=36): male + older age + RA-ILD + RF/ACPA positive + MTX non-user, Group C(n=35): RF/ACPA positive + absence of RA-ILD + MTX user, Group D (n=28): seronegative + MTX user + absence of RA-ILD + history of biologic DMARDs failure. The rate of JAKi-IR was A:9%, B:8%, C:20%, D:32%, and the significant difference between Group B and D was identified (p=0.02). In multiple comparison of 4 groups, no significant difference was identified (p=0.06) (Figure2).Conclusion:JAKi-IR would be more likely to be seronegative, MTX use, absence of RA-ILD and history of biologic DMARDs failure. Cluster analysis is an exploratory tool that aids in the analysis of huge amount of data.References:[1] Takeuchi T, Yamanaka H, Yamaoka K, Arai S, Toyoizumi S, DeMasi R, et al. Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data. Mod Rheumatol. 2019;29(5):756-66.[2] Tanaka Y, Atsumi T, Amano K, Harigai M, Ishii T, Kawaguchi O, et al. Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials. Mod Rheumatol. 2018;28(4):583-91.Disclosure of Interests:Masanari Sugawara: None declared, Yuichiro Fujieda: None declared, Atsushi Noguchi: None declared, Shun Tanimura: None declared, Yuka Shimizu: None declared, Ikuma Nakagawa: None declared, Michihito Kono: None declared, Masaru Kato: None declared, Kenji Oku: None declared, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc.

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