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Calcified Tissue International Nov 2022The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the... (Review)
Review
The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of "established therapeutics". An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.
Topics: Antirheumatic Agents; Biological Products; Bone Diseases, Metabolic; Bone and Bones; Glucocorticoids; Humans; Janus Kinase Inhibitors
PubMed: 35771255
DOI: 10.1007/s00223-022-01001-y -
BMJ (Clinical Research Ed.) Mar 2016
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans
PubMed: 27009280
DOI: 10.1136/bmj.i387 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2017Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate... (Review)
Review
Methotrexate-associated lymphproliferative disorder (MTX-LPD) is a rare but critical complication developing in patients treated with methotrexate. Now that methotrexate is an anchor drug in the management of rheumatoid arthritis and become commonly used, MTX-LPD cases have increased. Many things has been unclear such as incidence, demographic characters, and risk factors. However, as the researches increased, several interesting topics has been demonstrated like associations with Epsteiin-Barr virus and with cell-mediated immunity. This report reviews newly the latest findings and future challenges on MTX-LPD.
Topics: Age Factors; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Herpesvirus 4, Human; Humans; Immunity, Cellular; Lymphoproliferative Disorders; Male; Methotrexate; Prognosis; Risk Factors
PubMed: 28747604
DOI: 10.2177/jsci.40.174 -
Journal of Biomedical Materials... Apr 2021Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million... (Review)
Review
Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA-approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes. Despite the discovery of several disease-modifying OA drugs (DMOADs) and promising results in preclinical studies, their clinical translation has been significantly limited because of poor intra-articular (IA) bioavailability and challenges in delivering these compounds to tissues of interest within the joint. Here, we review current OA treatments and their effectiveness at reducing joint pain, as well as novel targets for OA treatment and the challenges related to their clinical translation. Moreover, we discuss intra-articular (IA) drug delivery as a promising route of administration, describe its inherent challenges, and review recent advances in biomaterial-based IA drug delivery for OA treatment. Finally, we highlight the potential of tissue targeting in the development of effective IA drug delivery systems.
Topics: Animals; Antirheumatic Agents; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Humans; Injections, Intra-Articular; Osteoarthritis
PubMed: 32780515
DOI: 10.1002/jbm.a.37074 -
Nature Reviews. Rheumatology Jan 2014Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the... (Review)
Review
Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Humans; Injections, Intra-Articular; Rheumatic Diseases; Time Factors
PubMed: 24189839
DOI: 10.1038/nrrheum.2013.159 -
Endocrine Regulations Apr 2022Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The...
Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Factors; Disease Progression; Humans; Prognosis
PubMed: 35489053
DOI: 10.2478/enr-2022-0016 -
Biochemical Pharmacology Jun 2018Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular protective processes. Rheumatic diseases are chronic conditions characterized by... (Review)
Review
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular protective processes. Rheumatic diseases are chronic conditions characterized by inflammation, pain, tissue damage and limitations in function. Main examples are rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis and osteoporosis. Their high prevalence constitutes a major health problem with an important social and economic impact. A wide range of evidence indicates that Nrf2 may control different mechanisms involved in the physiopathology of rheumatic conditions. Therefore, the appropriate expression and balance of Nrf2 is necessary for regulation of oxidative stress, inflammation, immune responses, and cartilage and bone metabolism. Numerous studies have demonstrated that Nrf2 deficiency aggravates the disease in experimental models while Nrf2 activation results in immunoregulatory and anti-inflammatory effects. These reports reinforce the increasing interest in the pharmacologic regulation of Nrf2 and its potential applications. Nevertheless, a majority of Nrf2 inducers are electrophilic molecules which may present off-target effects. In recent years, novel strategies have been sought to modulate the Nrf2 pathway which has emerged as a therapeutic target in rheumatic conditions.
Topics: Antirheumatic Agents; Gene Expression Regulation; Humans; Molecular Targeted Therapy; NF-E2-Related Factor 2; Rheumatic Diseases
PubMed: 29660314
DOI: 10.1016/j.bcp.2018.04.010 -
Nature Reviews. Rheumatology Mar 2018The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome,... (Review)
Review
The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.
Topics: Antirheumatic Agents; Clinical Trials as Topic; Gene Regulatory Networks; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Interferon Type I; Rheumatic Diseases; Signal Transduction
PubMed: 29559718
DOI: 10.1038/nrrheum.2018.31 -
Pharmacological Reports : PR 2006A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue... (Review)
Review
A variety of disease-modifying antirheumatic drugs (DMARDs) are available to control the clinical activity of rheumatoid arthritis (RA). Methotrexate (MTX), an analogue of folic acid and of aminopterin, is the most commonly used DMARD and is now prescribed worldwide to at least 500,000 patients with RA. The mechanism by which MTX used at a low dose modulates inflammation in RA is still unknown. Monitoring of the therapy in terms of MTX concentration in patients with RA seems not to have a significant influence on the effectiveness of the treatment. Two meta-analyses showed that MTX has one of the best efficacy/toxicity ratios. It should be the first DMARD used in the majority of patients with RA at this time. However, a significant number of patients treated only with MTX fail to achieve optimal disease control, so there are many combinations of DMARD regimes. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission. The therapy of RA is a dynamic process and requires maintaining a delicate balance between benefits and risks. Even with the newer biological agents, MTX continues to serve as a reference point and there is still a role for MTX in the treatment of RA patients.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Humans; Meta-Analysis as Topic; Methotrexate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16963793
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Jul 2022Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and... (Review)
Review
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Inflammation
PubMed: 35643074
DOI: 10.1016/j.biopha.2022.113126