Review

Authors: Josef S Smolen, Daniel Aletaha, Iain B McInnes...

Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Humans; Incidence

PubMed: 27156434
DOI: 10.1016/S0140-6736(16)30173-8

Review

Authors: Andrei-Flavius Radu, Simona Gabriela Bungau

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Models, Biological; Protein Kinase Inhibitors

PubMed: 34831081
DOI: 10.3390/cells10112857

Review

Authors: Yen-Ju Lin, Martina Anzaghe, Stefan Schülke...

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.

Topics: Animals; Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Cytokines; Humans; Inflammation; Models, Biological

PubMed: 32260219
DOI: 10.3390/cells9040880

Review

Authors: Amy M Wasserman

Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Combined Modality Therapy; Complementary Therapies; Diagnosis, Differential; Exercise Therapy; Humans; Prognosis; Risk Factors

PubMed: 22150658
DOI: No ID Found

Review

Authors: Di Wu, Yehao Luo, Tong Li...

As a systemic autoimmune disease, rheumatoid arthritis (RA) usually causes damage not only to joints, but also to other tissues and organs including the heart, kidneys, lungs, digestive system, eyes, skin, and nervous system. Excessive complications are closely related to the prognosis of RA patients and even lead to increased mortality. This article summarizes the serious complications of RA, focusing on its incidence, pathogenesis, clinical features, and treatment methods, aiming to provide a reference for clinicians to better manage the complications of RA.

Topics: Humans; Arthritis, Rheumatoid; Prognosis; Incidence

PubMed: 36618407
DOI: 10.3389/fimmu.2022.1051082

Review

Authors: Suha Kadura, Ganesh Raghu

Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation of RA being lung involvement. While essentially any of the lung compartments can be affected and manifest as interstitial lung disease (ILD), pleural effusion, cricoarytenoiditis, constrictive or follicular bronchiolitis, bronchiectasis, pulmonary vasculitis, and pulmonary hypertension, RA-ILD is a leading cause of death in patients with RA and is associated with significant morbidity and mortality. In this review, we focus on the common pulmonary manifestations of RA, RA-ILD and airway disease, and discuss evolving concepts in the pathogenesis of RA-associated pulmonary fibrosis, as well as therapeutic strategies, and have revised our previous review on the topic. A rational clinical approach for the diagnosis and management of RA-ILD, as well as an approach to patients with clinical worsening in the setting of treatment with disease-modifying agents, is included. Future directions for research and areas of unmet need in the realm of RA-associated lung disease are raised.

Topics: Arthritis, Rheumatoid; Bronchiectasis; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Pulmonary Fibrosis

PubMed: 34168062
DOI: 10.1183/16000617.0011-2021

Review

Authors: Sunhee Jang, Eui-Jong Kwon, Jennifer Jooha Lee...

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

Topics: Animals; Arthritis, Rheumatoid; Biomarkers; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Immune System; Molecular Diagnostic Techniques; Prognosis; Treatment Outcome

PubMed: 35055087
DOI: 10.3390/ijms23020905

Review

Authors: Jie Huang, Xuekun Fu, Xinxin Chen...

Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.

Topics: Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Epigenesis, Genetic; Humans

PubMed: 34305919
DOI: 10.3389/fimmu.2021.686155

Review

Authors: Gene-Siew Ngian

BACKGROUND

Rheumatoid arthritis is a chronic disease that can cause irreversible joint damage and significant disability. With a prevalence of 1%, it has a considerable cost to the community. Diagnosis is based on a combination of clinical and laboratory features. Patients typically present with a symmetrical polyarthritis of the small joints of the hands and feet accompanied by early morning stiffness and, occasionally, constitutional symptoms.

OBJECTIVE

This review discusses the role of the general practitioner in the diagnosis and early management of rheumatoid arthritis.

DISCUSSION

It is increasingly recognised that there is a 'window of opportunity' within which disease modifying antirheumatic drug therapy should be commenced to arrest progressive disease and joint destruction. Methotrexate is usually the first line agent in the management of rheumatoid arthritis but simple analgesia and nonsteroidal anti-inflammatory drugs are also important for symptom control.

Topics: Adrenal Cortex Hormones; Antirheumatic Agents; Arthritis, Rheumatoid; Australia; Biomarkers; Diagnosis, Differential; Fatty Acids, Omega-3; Humans; Practice Guidelines as Topic

PubMed: 20877764
DOI: No ID Found

Review

Authors: Bryant R England, Geoffrey M Thiele, Daniel R Anderson...

Rheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.

Topics: Arthritis, Rheumatoid; Autoimmunity; Cardiovascular Diseases; Humans; Patient Care Management; Risk Assessment; Risk Factors

PubMed: 29685876
DOI: 10.1136/bmj.k1036