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Frontiers in Immunology 2023Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to... (Review)
Review
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Sjogren's Syndrome; Cytokines
PubMed: 37809072
DOI: 10.3389/fimmu.2023.1150661 -
Current Opinion in Rheumatology Sep 2021
Topics: Antirheumatic Agents; COVID-19; Humans; Rheumatic Diseases; Rheumatology; SARS-CoV-2
PubMed: 34175865
DOI: 10.1097/BOR.0000000000000813 -
Rheumatic Diseases Clinics of North... Feb 2022Despite an increase in the number of available therapeutics, many children with rheumatic disease continue to experience active inflammatory disease and treatment... (Review)
Review
Despite an increase in the number of available therapeutics, many children with rheumatic disease continue to experience active inflammatory disease and treatment failure. One reason for treatment failure is the lack of dosing paradigms to account for the wide between-patient variability in drug pharmacokinetics because of developmental changes or genetic polymorphisms that effect drug absorption, distribution, metabolism, and elimination. This review highlights several strategies to optimize dosing for biologic and nonbiologic disease-modifying antirheumatic drugs, including therapeutic drug monitoring, pharmacogenomics, and the use of pharmacokinetic/pharmacodynamic modeling.
Topics: Antirheumatic Agents; Child; Humans; Pharmacogenetics; Precision Medicine; Rheumatic Diseases; Rheumatology
PubMed: 34798954
DOI: 10.1016/j.rdc.2021.09.010 -
Frontiers in Immunology 2023Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the... (Review)
Review
Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the disease relapse rates are high. Recent clinical trials on biological disease-modifying anti-rheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors have demonstrated their efficacy in reducing LVV relapse rates and GC dosages. However, the control of residual inflammation and degenerative alterations in the vessel wall remains an outstanding requirement in the clinical management of LVV. The analysis of immune cell phenotypes in patients with LVV may predict their response to treatment with bDMARDs and JAK inhibitors and guide their optimal use. In this mini-review, we focused on molecular markers, including the immune cell proportions and gene expression, in patients with LVV and in mouse models of LVV treated with bDMARDs and JAK inhibitors.
Topics: Animals; Mice; Janus Kinase Inhibitors; Antirheumatic Agents; Giant Cell Arteritis; Takayasu Arteritis; Recurrence
PubMed: 37197652
DOI: 10.3389/fimmu.2023.1197342 -
American Journal of Ophthalmology Nov 2020To describe the rationale for revising the hydroxychloroquine (HCQ) dosing and screening guidelines and to identify the barriers to more effective guidelines in the... (Review)
Review
PURPOSE
To describe the rationale for revising the hydroxychloroquine (HCQ) dosing and screening guidelines and to identify the barriers to more effective guidelines in the future.
DESIGN
Literature review.
METHODS
A PubMed query of studies on HCQ dosing and HCQ retinopathy (HCQR) screening was conducted with a selective review of the English language literature.
RESULTS
Three iterations of the American Academy of Ophthalmology HCQ dosing and HCQR screening guidelines have been published without including prescribing physicians on the writing committees. This may contribute to prescribing physicians' low adherence to the guidelines. As ancillary tests have improved, asymptomatic HCQR is being detected earlier, leading to a higher reported prevalence of HCQR and a drop in the ceiling for safe dosing. These trends put stricter constraints on prescribers and their patients, who may have had well-controlled autoimmune disease on HCQ doses that were previously considered to be below the high-risk threshold for HCQR. Indeed, stopping HCQ at the earliest sign of HCQR should be reconsidered; for cases of early HCQR, dose reduction and more intensive monitoring for retinopathy may strike a more appropriate balance between HCQ risk and benefits. A prospective study using the Diabetic Retinopathy Clinical Research Retina Network with standardized collection of data, HCQ blood levels, centralized grading of ancillary tests, and community and academic ophthalmologists would provide a stronger evidence base for future HCQ guidelines.
CONCLUSIONS
The HCQ dosing and screening guidelines should be updated and a prospective study of HCQ dosing and HCQR should be initiated with the joint efforts of ophthalmologists and prescribing physicians.
Topics: Antirheumatic Agents; Diagnostic Techniques, Ophthalmological; Humans; Hydroxychloroquine; Ophthalmology; Practice Guidelines as Topic; Prospective Studies; Retinal Diseases; Risk Assessment
PubMed: 32610049
DOI: 10.1016/j.ajo.2020.06.030 -
Phytomedicine : International Journal... Jul 2023To assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic... (Clinical Trial)
Clinical Trial
OBJECTIVE
To assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic profiling were performed to reveal the potential mechanisms.
METHODS
Patients were enrolled in an open-label, Simon 2-stage, single-center, single-arm trial at Guangdong Provincial Hospital of Chinese Medicine. Main inclusion criteria were defined as follows: Aged 18 to 70, low to medium disease activity, fulfilled the RA classification criteria of EULAR/ACR 2010. Patients received the oral medication of MTX 10-15 mg weekly and natural product granules twice a day. Primary outcome was the American College of Rheumatology (ACR) 20% preliminary definition of improvement. Single-cell RNA sequencing(scRNA-seq) on peripheral blood mononuclear cells (PBMCs) was used to show the aberrant metabolism before and after the trial. Plasma lipidomic profiling quantified the lipid changes caused by this MTX-based therapy. Finally, post-hoc analysis on responders and non-responders were used for further analysis.
RESULTS
Between October 2020 and June 2022, 46 patients received treatment, while 42 finished follow-ups. 27 of 46 (58.70%) patients achieved ACR20, and significant changes were observed in several secondary outcomes. Comparative scRNA-seq analysis before and after the treatment revealed that lipidomic metabolism was broadly downregulated. Plasma lipidomic profiling reveals that 40 lipids were observed significantly changed. Post-hoc analysis showed the lipid changes were separately linked to clinical parameters in responders and non-responders.
CONCLUSION
The study reveals that the combination therapy of HQT+MTX is effective and has a certain correlation with lipid metabolism, but more rigorous study design is still needed to confirm this speculation.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Leukocytes, Mononuclear; Lipidomics; Lipids; Methotrexate; Transcriptome; Treatment Outcome
PubMed: 37094424
DOI: 10.1016/j.phymed.2023.154816 -
Lancet (London, England) Jun 2022
Topics: Antirheumatic Agents; Colitis, Ulcerative; Heterocyclic Compounds, 3-Ring; Humans; Janus Kinase Inhibitors
PubMed: 35644164
DOI: 10.1016/S0140-6736(22)00778-4 -
Nature Reviews. Rheumatology Nov 2022
Topics: Humans; Leukocyte L1 Antigen Complex; Antibodies, Monoclonal, Humanized; Antirheumatic Agents
PubMed: 36163436
DOI: 10.1038/s41584-022-00851-y -
The Medical Clinics of North America Mar 2021
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Rheumatology
PubMed: 33589111
DOI: 10.1016/j.mcna.2021.01.001 -
Ageing Research Reviews Jun 2023Rheumatoid arthritis (RA) is a heterogeneous autoimmune inflammatory disorder defined by the damage to the bone and cartilage in the synovium, which causes joint... (Review)
Review
Rheumatoid arthritis (RA) is a heterogeneous autoimmune inflammatory disorder defined by the damage to the bone and cartilage in the synovium, which causes joint impairment and an increase in the mortality rate. It is associated with an incompletely elucidated pathophysiological mechanism. Even though disease-modifying antirheumatic drugs have contributed to recent improvements in the standard of care for RA, only a small fraction of patients is able to attain and maintain clinical remission without the necessity for ongoing immunosuppressive drugs. The evolution of tolerance over time as well as patients' inability to respond to currently available therapy can alter the overall management of RA. A significant increase in the research of RA nano therapies due to the possible improvements they may provide over traditional systemic treatments has been observed. New approaches to getting beyond the drawbacks of existing treatments are presented by advancements in the research of nanotherapeutic techniques, particularly drug delivery nano systems. Via passive or active targeting of systemic delivery, therapeutic drugs can be precisely transported to and concentrated in the affected sites. As a result, nanoscale drug delivery systems improve the solubility and bioavailability of certain drugs and reduce dose escalation. In the present paper, we provide a thorough overview of the possible biomedical applications of various nanostructures in the diagnostic and therapeutic management of RA, derived from the shortcomings of conventional therapies. Moreover, the paper suggests the need for improvement on the basis of research directions and properly designed clinical studies.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Drug Delivery Systems; Longitudinal Studies
PubMed: 37031724
DOI: 10.1016/j.arr.2023.101927