scholarly journals Rheumatoid Arthritis: A Novel Approach in Diagnosis and Treatment

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Marina Kostic
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Changes ◽  
Interleukin 1 ◽  
Treat To Target ◽  
Signal Pathways ◽  
Biological Drugs ◽  
Safety Issues ◽  
Novel Approach ◽  
Post Marketing ◽  
Factor Α

AbstractThe rheumatoid arthritis is chronic disease with progressive course and deteriorations of joints as well as other organs. The pathogenesis of rheumatoid arthritis is characterized with chronic synovitis and inflammation. The main roles in development of rheumatoid arthritis have auto-reactive T cells and inflammatory cytokines, especially tumor necrosis factor α, interleukin 1 and interleukin 6. The management of rheumatoid arthritis has evolved significantly in the past twenty years, especially with introduction new diagnostic criteria by European League for Rheumatoid Arthritis which are very sensitive for early arthritis. The main goal of treating rheumatoid arthritis is to start with therapy in the phase of the disease when destruction of joints can still be prevented. Therapeutic strategies for rheumatoid arthritis involve wide palette of different drugs which can be divided into conventional and biological Disease Modifying Anthirheumatic Drugs. The use of methotrexate in combination with biological drugs provide targeting not only structural changes in rheumatoid arthritis but also and immunological pathways in development of rheumatoid arthritis. These drugs synergistically provide clinical remission and low activity of rheumatoid arthritis in the majority of patients. The uses of biological drugs are limited due their high costs or safety profile. In order to reduce costs and toxicity in the treatment of rheumatoid arthritis, new treat- to –target concept is established. The new class of drugs which modulate signal pathways and activity of tyrosine kinase are under investigations in post marketing surveys in patients with rheumatoid arthritis as in efficacy as in safety issues.

scholarly journals THU0206 А VERY EARLY (7-28 DAYS) RESPONSE ON JAK INHIBITOR TOFACITINIB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: EFFECT ON PAIN AND CENTRAL SENSITIZATION.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.3-327
Author(s):  
A. Karateev ◽  
E. Filatova ◽  
E. Pogozheva ◽  
V. Amirdzhanova ◽  
E. Nasonov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Central Sensitization ◽  
Early Time ◽  
National Registry ◽  
Genetically Engineered ◽  
Pain Severity ◽  
Signal Pathways ◽  
Jak Inhibitor ◽  
Jak Inhibitors ◽  
Biological Drugs

Background:The presence of central sensitization (CS) significantly burdens the course of rheumatoid arthritis (RA). JAK inhibitors block intracellular signal pathways including the ones responsible for synthesis of mediators and cytokines causing pain and CS. The application of JAK inhibitors is supposed to relieve pain and reduce CS severity promptly.Objectives:To evaluate JAK inhibitor effect on pain and signs of CS in patients with active RA 7 and 28 days after the start of therapy.Methods:Study group included 39 patients with RA, their age was 50.9±11.1, 79.5% of women, 89.7% of RF “+”, DAS28 5.8±0.6, receiving DMARDs (methotrexate 82.0% and leflunomide 18.0%), who were administered with tofacitinib 5 mg 2 times a day due to inefficiency or intolerance of genetically engineered biological drugs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration.Results:Patients initially experienced a severe pain – 5.72±2.21 according to the visual analogue scale (VAS), 53.8% had signs of central sensitization (CSI ≥ 40), 17.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.37±2.2 (р=0.01), pain decrease of 29.4±17.9% (BPI), NCP – PainDETECT from 12.9±5.5 to 10.6±5.6 (р=0.047) and CS – CSI from 43.1±12.8 to 35.9±11.2 (р=0.01). The effect had increased after 28 days: pain level (VAS) was 2.84±1.57 (р=0.000), pain decrease of 43.6±29.6% (BPI), PainDETECT 29.8±12.4 (р=0.000), CSI 26.4±13.9 (р=0.000).During this period there were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect, also due to impact on CS and NCP.Source: National Registry patients with RADisclosure of Interests: :Andrey Karateev: None declared, Ekaterina Filatova: None declared, Elena Pogozheva: None declared, Vera Amirdzhanova: None declared, Evgeny Nasonov: None declared, Alexander Lila: None declared, V Mazurov: None declared, N Lapkina: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Tatiana Salnikova: None declared, Ruzana Samigullina: None declared, Diana Chakieva: None declared, Irina Marusenko: None declared, Olga Semagina: None declared, Marina Semchenkova: None declared

Carotid Plaque Is Not Associated With Increased Levels of Interleukin 1, Interleukin 6, and Tumor Necrosis Factor α in Rheumatoid Arthritis

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Rosa I. Arvizu-Rivera ◽  
Jose R. Azpiri-Lopez ◽  
Iris J. Colunga-Pedraza ◽  
Jesus A. Cardenas-de la Garza ◽  
Raymundo Vera-Pineda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Carotid Plaque ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 1 ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice

2000 ◽  
Vol 191 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Reiko Horai ◽  
Shinobu Saijo ◽  
Hidetoshi Tanioka ◽  
Susumu Nakae ◽  
Katsuko Sudo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Type Ii Collagen ◽  
Cytokine Network ◽  
Gene Deficiency ◽  
Double Stranded Dna ◽  
Inflammatory Arthropathy ◽  
Factor Α ◽  
Deficient Mice

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra–deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB/cA background, but not those on a C57BL/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor α were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.

scholarly journals Pharmacovigilance of Biopharmaceuticals in Rheumatic Diseases, Adverse Events, Evolution, and Perspective: An Overview

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 303
Author(s):  
Sandra Rodríguez ◽  
Andrés Muñoz ◽  
Rosa-Helena Bustos ◽  
Diego Jaimes
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Adverse Events ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Cell Mediated Immunity ◽  
Systemic Lupus ◽  
Biological Drugs ◽  
Necrosis Factor Alpha ◽  
Post Marketing

Since we have gained an understanding of the immunological pathophysiology of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, treatment based on biological drugs has become a fundamental axis. These therapies are oriented towards the regulation of cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1, and the modulation of cell-mediated immunity (B cells and T cells) by anti CD20 or anti CTAL-4 agents, and can increase the risk of associated infections or adverse events (AE). In this context, the entry of biotherapeutics represented a challenge for pharmacovigilance, risk management and approval by the main global regulatory agencies regarding biosimilars, where efficacy and safety are based on comparability exercises without being an exact copy in terms of molecular structure. The objective of this review is divided into three fundamental aspects: (i) to illustrate the evolution and focus of pharmacovigilance at the biopharmaceutical level, (ii) to describe the different approved recommendations of biopharmaceuticals (biological and biosimilars) and their use in rheumatic diseases (RDs) such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE) and other less frequent RD like cryopyrin-associated autoinflammatory syndromes (CAPS), and (iii) to identify the main AE reported in the post-marketing phase of RD biopharmaceuticals.

scholarly journals Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis

2011 ◽  
Vol 38 (5) ◽  
pp. 835-845 ◽  
Author(s):  
ROBERT LAUNOIS ◽  
BERNARD AVOUAC ◽  
FRANCIS BERENBAUM ◽  
OLIVIER BLIN ◽  
ISABELLE BRU ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 1 ◽  
Certolizumab Pegol ◽  
Inadequate Response ◽  
Acr20 Response ◽  
Multiple Treatment ◽  
American College Of Rheumatology ◽  
Significant Efficacy ◽  
Treatment Comparisons ◽  
Factor Α

Objective.To compare the clinical efficacy of certolizumab pegol (CZP) with that of other anticytokine agents indicated for the treatment of rheumatoid arthritis (RA) with identical therapeutic indication (anti-tumor necrosis factor-α, anti-interleukin 1 or 6), with the objective of determining the noninferiority of CZP.Methods.A systematic review was performed to identify randomized controlled trials that assessed the efficacy of anticytokine agents in combination with conventional disease-modifying antirheumatic drugs (DMARD) after 6 months of treatment, using the American College of Rheumatology (ACR) response criteria, in patients with RA who have shown inadequate response to DMARD including methotrexate. Indirect treatment comparisons were carried out by a multiple-treatment Bayesian random-effects metaanalysis. Data were analyzed using the Markov chain Monte Carlo simulation. Noninferiority of CZP was assessed in comparison with a predefined equivalence margin of 5%.Results.Nineteen placebo-controlled studies were identified: 14 evaluated the efficacy of 5 anti-TNF-α agents (infliximab, etanercept, adalimumab, golimumab, CZP) and 5 evaluated efficacy of 2 anti-interleukin agents (anakinra, tocilizumab). Every treatment showed significant efficacy versus placebo in individual studies. The multiple-treatment metaanalysis showed a highest OR for CZP on ACR20 response. Metaanalysis indicates that the efficacy of CZP according to ACR20 response is superior to that of infliximab, adalimumab, and anakinra, and equivalent or superior to that of etanercept, golimumab, and tocilizumab. According to ACR50 response, the efficacy of CZP is equivalent or superior to that of all other anticytokines.Conclusion.Results of this original multiple-treatment Bayesian metaanalysis indicate that certolizumab pegol is at least as efficacious as the preexisting antirheumatic anticytokine biotherapies.

Circulating Dickkopf-1 Is Correlated with Bone Erosion and Inflammation in Rheumatoid Arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 821-827 ◽  
Author(s):  
SHI-YAO WANG ◽  
YAN-YING LIU ◽  
HUA YE ◽  
JIAN-PING GUO ◽  
RU LI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Healthy Controls ◽  
Serum Samples ◽  
Reactive Protein ◽  
Tnf Α ◽  
Factor Α ◽  
Dickkopf 1

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

Molecular therapeutic targets in rheumatoid arthritis

2005 ◽  
Vol 7 (16) ◽  
pp. 1-20 ◽  
Author(s):  
Sandra M. Sacre ◽  
Evangelos Andreakos ◽  
Peter Taylor ◽  
Marc Feldmann ◽  
Brian M. Foxwell
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Investigation ◽  
Interleukin 1 ◽  
Therapeutic Targets ◽  
Disease Process ◽  
New Drugs ◽  
Therapeutic Modalities ◽  
Molecular Aspects ◽  
Molecular Therapeutic ◽  
Factor Α

In an attempt to combat the pain and damage generated by rheumatoid arthritis (RA), new drugs are being developed to target molecular aspects of the disease process. Recently, a major development has been the use of biologicals (antibodies and soluble receptors) that neutralise the activity of tumour necrosis factor α (TNF-α) and interleukin 1 (IL-1), both of which are involved in disease progression. An increase in our understanding of cell and molecular biology has resulted in the identification and investigation of potential new targets, and also the refinement and improvement of current therapeutic modalities. This review describes therapies that are approved, in clinical trials or under pre-clinical investigation at the laboratory level, particularly focusing on cytokines, although other therapeutic targets of interest are mentioned.

scholarly journals Psoriatic arthritis: pathogenetic features and innovative therapies

2019 ◽  
Vol 56 (6) ◽  
pp. 685-691 ◽  
Author(s):  
A. M. Lila ◽  
E. L. Nasonov ◽  
T. V. Korotaeva
Keyword(s):  
Psoriatic Arthritis ◽  
Clinical Manifestations ◽  
Treat To Target ◽  
Management Decision ◽  
High Tech ◽  
Biological Drugs ◽  
Basic Principles ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α

The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- and anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.

Sign in / Sign up

Export Citation Format

Share Document