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Lancet (London, England) Nov 2023Rheumatoid arthritis is a chronic, systemic, autoimmune inflammatory disease that mainly affects the joints and periarticular soft tissues. In this Seminar, we provide... (Review)
Review
Rheumatoid arthritis is a chronic, systemic, autoimmune inflammatory disease that mainly affects the joints and periarticular soft tissues. In this Seminar, we provide an overview of the main aspects of rheumatoid arthritis. Epidemiology and advances in the understanding of rheumatoid arthritis pathogenesis will be reviewed. We will discuss the clinical manifestations of rheumatoid arthritis, classification criteria, and the value of imaging in the diagnosis of the disease. The advent of new medications and the accumulated scientific evidence demand continuous updating regarding the diagnosis and management, including therapy, of rheumatoid arthritis. An increasing number of patients are now able to reach disease remission. This major improvement in the outcome of patients with rheumatoid arthritis has been determined by a combination of different factors (eg, early diagnosis, window of opportunity, treat-to-target strategy, advent of targeted disease-modifying antirheumatic drugs, and combination therapy). We will discuss the updated recommendations of the two most influential societies for rheumatology worldwide (ie, the American College of Rheumatology and European Alliance of Associations for Rheumatology) for the management of rheumatoid arthritis. Furthermore, controversies (ie, the role of glucocorticoids in the management of rheumatoid arthritis and safety profile of Janus kinase inhibitors) and outstanding research questions, including precision medicine approach, prevention, and cure of rheumatoid arthritis will be highlighted.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Glucocorticoids; Rheumatology; Janus Kinase Inhibitors
PubMed: 38240831
DOI: 10.1016/S0140-6736(23)01525-8 -
BMJ (Clinical Research Ed.) Jan 2024Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness... (Review)
Review
Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness that typically affects symmetrically distributed small and large joints. Without effective treatment, significant joint damage, disability, and work loss develop, owing to chronic inflammation of the joint lining (synovium). Over the past 25 years, the management of this condition has been revolutionized, resulting in substantially higher levels of disease remission and better long term outcomes. This improvement reflects a paradigm shift towards early and aggressive pharmacological intervention coupled with a proliferation in treatment choice, in turn related to enhanced pathobiological understanding and the advent of new drugs for rheumatoid arthritis. Following an overview of these developments from a historical perspective, and with a general audience in mind, this review focuses on newer, targeted treatments in an ever evolving landscape. The review highlights ongoing areas of debate and unmet need, including the proportion of patients with persistent, difficult-to-treat disease, despite recent advances. Also discussed are personalized, strategic approaches to individual patients, the role for imaging in clinical decision making, and the goal of sustained, drug free remission and disease prevention in the future.
Topics: Humans; Arthritis, Rheumatoid; Inflammation; Diagnostic Imaging; Treatment Outcome; Antirheumatic Agents
PubMed: 38233032
DOI: 10.1136/bmj-2022-070856 -
Clinical Rheumatology Sep 2023Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality... (Review)
Review
Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality CPG recommendations, highlighting areas of consistency, and inconsistency. Electronic searches of five databases and four online guideline repositories were performed. RA management CPGs were eligible for inclusion if they were written in English and published between January 2015 and February 2022; focused on adults ≥ 18 years of age; met the criteria of a CPG as defined by the Institute of Medicine; and were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II instrument. RA CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organization of care and did not include interventional management recommendations; and/or included other arthritic conditions. Of 27 CPGs identified, 13 CPGs met eligibility criteria and were included. Non-pharmacological care should include patient education, patient-centered care, shared decision-making, exercise, orthoses, and a multi-disciplinary approach to care. Pharmacological care should include conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), with methotrexate as the first-line choice. If monotherapy conventional synthetic DMARDs fail to achieve a treatment target, this should be followed by combination therapy conventional synthetic DMARDs (leflunomide, sulfasalazine, hydroxychloroquine), biologic DMARDS and targeted synthetic DMARDS. Management should also include monitoring, pre-treatment investigations and vaccinations, and screening for tuberculosis and hepatitis. Surgical care should be recommended if non-surgical care fails. This synthesis offers clear guidance of evidence-based RA care to healthcare providers. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/UB3Y7 ).
Topics: Adult; Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hydroxychloroquine; Methotrexate; Sulfasalazine; Practice Guidelines as Topic
PubMed: 37291382
DOI: 10.1007/s10067-023-06654-0 -
Medicina (Kaunas, Lithuania) Oct 2023Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA... (Review)
Review
Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.
Topics: Aged; Humans; Male; Middle Aged; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Treatment Outcome
PubMed: 37893596
DOI: 10.3390/medicina59101878 -
Nature Reviews. Rheumatology Feb 2024Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA).... (Review)
Review
Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA). There has been debate about their safety, particularly following the issuance of guidance by regulatory agencies advising caution in their use in certain patients. The registrational clinical trials and registry data of JAK inhibitors did not identify a difference in the risk of major adverse cardiovascular events (MACEs), venous thromboembolism, malignancies or infections (other than herpes zoster) with a JAK inhibitor versus a biologic DMARD. In the ORAL Surveillance trial, which enrolled patients >50 years of age with ≥1 cardiovascular risk factor, tofacitinib was statistically inferior to TNF inhibitors for the occurrence of MACEs and malignancy. Further post hoc analysis of the data revealed that an age of ≥65 years, a high baseline cardiovascular risk, a history of smoking, sustained inflammation, disease activity and suboptimal treatment of cardiovascular comorbidities all increase the risk of these outcomes. The guidance issued by regulatory agencies should be carefully considered to ensure appropriate and safe treatment of patients with RA without undertreatment of patients who might benefit from JAK inhibitor, as well as biologic, treatment. As always, the risks associated with the use of these agents, treatment goals, costs and patient preferences should be discussed with the patient.
Topics: Humans; Aged; Janus Kinase Inhibitors; Arthritis, Rheumatoid; Antirheumatic Agents; Neoplasms; Biological Products
PubMed: 38216757
DOI: 10.1038/s41584-023-01062-9 -
JAAPA : Official Journal of the... Sep 2023Rheumatoid arthritis (RA) affects about 1% of the world's population and can lead to loss of joint function, reduced mobility, and permanent damage to cartilage and... (Review)
Review
Rheumatoid arthritis (RA) affects about 1% of the world's population and can lead to loss of joint function, reduced mobility, and permanent damage to cartilage and bone. Treatment options for RA primarily include disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, but the development of new drugs has complicated treatment decisions. Weighing treatment options for patients with RA largely depends on three major factors: efficacy, adverse reaction profile, and cost. A review of the literature supports methotrexate monotherapy as the current best-practice model for treating RA, compared with combination therapy of methotrexate and/or other DMARDs.
Topics: Humans; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; Combined Modality Therapy
PubMed: 37668490
DOI: 10.1097/01.JAA.0000937316.70181.ff -
Autoimmunity Reviews Jul 2023Rheumatoid Arthritis (RA) is a progressive autoimmune disease. It is among the most widespread chronic illnesses in children, with an annual incidence of 1.6 to 23 new... (Review)
Review
Rheumatoid Arthritis (RA) is a progressive autoimmune disease. It is among the most widespread chronic illnesses in children, with an annual incidence of 1.6 to 23 new instances per 100,000 adolescents. About 1 child in every 1000 develops Juvenile Idiopathic Arthritis (JIA) type of chronic arthritis. The cause of JIA is not well known but what known is that it involves inflammation of the synovium and destruction of tissues in joints which can cause early-onset of oligo articular JIA. It is challenging to diagnose the condition in some children who initially complain of pain and joint swelling as there is no blood test discovered that can confirm the diagnoses of JIA. As JIA patients are immunosuppressed due to the use of drugs, making them vulnerable to catch infections like COVID-19 which can lead to cardiovascular diseases having high rate of morbidity and mortality. The comorbidity like Diabetes has higher incidence in these patients resulting in synergistic effect on inflammation. Currently, the connection of genetics in JIA provides evidence that HLA Class I and II alleles have a role in the pathophysiology of various subtypes of JIA which includes inflammation in the axial skeletal. The primary objective of therapy in juvenile idiopathic arthritis is the suppression of clinical symptoms. The pharmacological approach includes use of medications like DMARDs, NSAIDs etc. and non-pharmacological approach includes physiotherapy, which helps in restoring normal joint function and herbs as adjuvants which has the benefit of no side effects.
Topics: Child; Adolescent; Humans; Arthritis, Juvenile; COVID-19; Antirheumatic Agents; Arthritis, Rheumatoid; Inflammation
PubMed: 37068698
DOI: 10.1016/j.autrev.2023.103337 -
Best Practice & Research. Clinical... Sep 2023"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone... (Review)
Review
"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone formation. Recent years have witnessed the effectiveness of treatments, including biologics and nonsteroidal anti-inflammatory drugs, in managing axSpA symptoms. Emerging evidence points toward their potential impact on slowing structural disease progression. This comprehensive review centers on the pivotal role of inhibiting new bone formation in axSpA disease modification. It delves into the significance of imaging techniques for assessing disease progression and explores the disease-modifying properties of available axSpA treatments, encompassing NSAIDs, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors. This article offers valuable insights into the evolving landscape of disease modification strategies in axial spondyloarthritis, highlighting the multifaceted approaches used to attain these objectives.
Topics: Humans; Spondylitis, Ankylosing; Antirheumatic Agents; Spondylarthritis; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis; Disease Progression
PubMed: 38042689
DOI: 10.1016/j.berh.2023.101898 -
Rheumatology (Oxford, England) Feb 2024Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory... (Review)
Review
Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib.
Topics: Humans; Janus Kinase Inhibitors; Antirheumatic Agents; Arthritis, Rheumatoid; Janus Kinases; Psoriasis
PubMed: 37624925
DOI: 10.1093/rheumatology/kead448 -
Arthritis Research & Therapy Sep 2023Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study.
BACKGROUND
Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.
METHODS
Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.
RESULTS
Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.
CONCLUSIONS
Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.
TRIAL REGISTRATION
NCT02049138.
Topics: Humans; Antirheumatic Agents; Biological Therapy; Heterocyclic Compounds, 3-Ring; Spondylarthritis; Spondylitis, Ankylosing; Tumor Necrosis Factor Inhibitors
PubMed: 37723577
DOI: 10.1186/s13075-023-03128-1