Is There a Renaissance of Glucocorticoids in Rheumatoid Arthritis?

Kirwan, John R.; Gunasekera, Wiranthi

doi:10.1002/cpt.753

Cited by 8 publications

(7 citation statements)

References 4 publications

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“…However, there is no consensus on the optimal duration of treatment with glucocorticoids due to varying findings of the degree of adverse effects. [34] Combination therapy with GCs and DMARDs has led to quick remission, substantial delay in disease progression, and excellent protection against cartilage and bone erosion. [35] The clinical importance of glucocorticoids in treating RA must be clarified, considering that a few studies on the administration of GCs alone reported excellent alleviation of RA but failed to provide con-vincing evidence, respectively.…”

Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

“…[35] The clinical importance of glucocorticoids in treating RA must be clarified, considering that a few studies on the administration of GCs alone reported excellent alleviation of RA but failed to provide con-vincing evidence, respectively. [34,35] In addition, several adverse effects of higher glucocorticoid dosages have been reported, including bone loss and high-risk fractures. Patients with glucocorticoids at low doses over the long term have also exhibited other adverse effects, such as susceptibility to infection, alterations in glucose metabolism, cutaneous atrophy, cataract formation, and proximal myopathy.…”

Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

“…Patients with glucocorticoids at low doses over the long term have also exhibited other adverse effects, such as susceptibility to infection, alterations in glucose metabolism, cutaneous atrophy, cataract formation, and proximal myopathy. [34] Although the application of NSAIDs, DMARDs, and GCs exhibits therapeutic effects for symptom relief, long-term use of these drugs can cause severe adverse effects. Systemic absorption/distribution may lead to unexpected accumulation in nontarget organs, tissues, or cells and result in toxicity effects.…”

Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

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Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

Chen

Wang

Lee

et al. 2021

Adv Healthcare Materials

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Noninfectious arthritis (NIA) comprises a class of chronic and progressive inflammatory disorders that require early-stage management to prevent disease progression. The most common forms include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gouty arthritis. Current treatments involve nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs and glucocorticoids to alleviate clinical symptoms, although regular use of these can result in a high risk of chronic kidney disease and heart failure, as well as severe adverse gastrointestinal effects. Nanomedicine offers unique opportunities to address these challenges and improve therapeutic efficacy due to its ability to deliver therapeutics locally in a sustained manner, thus extending the half-life, improving bioavailability, and reducing the side effects of these agents. This review includes a comprehensive analysis of the mechanisms of various treatment options for NIA and highlights recent progress and emerging strategies in treating NIA with nanomedicine platforms, particularly related to long-term biosafety and nonspecific targeting in designing nanomedicine delivery systems.

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Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

Section: Tsdmards Jak Inhibitormentioning

confidence: 99%

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Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

Chen

Wang

Lee

et al. 2021

Adv Healthcare Materials

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“…Corticosteroids (CS) are a class of pleiotropic immunosuppressive agents used in the treatment of various inflammatory and autoimmune diseases, such as asthma (Barnes, 1998) and rheumatoid arthritis (Kirwan and Gunasekera, 2017). Their potent immunosuppressive properties also form the basis for their use in preventing rejection of solid organ transplants (Taylor et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Modeling Corticosteroid Pharmacogenomics and Proteomics in Rat Liver

Ayyar

Sukumaran

DuBois

et al. 2018

J Pharmacol Exp Ther

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Corticosteroids (CS) regulate the expression of numerous genes at the mRNA and protein levels. The time course of CS pharmacogenomics and proteomics were examined in livers obtained from adrenalectomized rats given a 50-mg/kg bolus dose of methylprednisolone. Microarrays and mass spectrometry-based proteomics were employed to quantify hepatic transcript and protein dynamics. One-hundred, sixty-three differentially expressed mRNA and their corresponding proteins (163 genes) were clustered into two dominant groups. The temporal profiles of most proteins were delayed compared with their mRNA, attributable to synthesis delays and slower degradation kinetics. On the basis of our fifth-generation model of CS, mathematical models were developed to simultaneously describe the emergent time patterns for an array of steroid-responsive mRNA and proteins. The majority of genes showed time-dependent increases in mRNA and protein expression before returning to baseline. A model assuming direct, steroid-mediated stimulation of mRNA synthesis was applied. Some mRNAs and their proteins displayed down-regulation following CS. A model assuming receptor-mediated inhibition of mRNA synthesis was used. More complex patterns were observed for other genes (e.g., biphasic behaviors and opposite directionality in mRNA and protein). Models assuming either stimulation or inhibition of mRNA synthesis coupled with dual secondarily induced regulatory mechanisms affecting mRNA or protein turnover were derived. These findings indicate that CS-regulated gene expression manifested at the mRNA and protein levels are controlled via mechanisms affecting key turnover processes. Our quantitative models of CS pharmacogenomics were expanded from mRNA to proteins and provide extended hypotheses for understanding the direct, secondary, and downstream mechanisms of CS actions.

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“…Initially, glucocorticoids showed stunning effects, but it rapidly became clear that an uncritical use causes severe long‐term adverse events, best documented for the iatrogenic Cushing syndrome. In their interesting Opinion article, Kirwan and Gunasekera question if there is “a renaissance of glucocorticoids in rheumatoid arthritis?” They conclude that combined therapy using conventional disease‐modifying antirheumatic drugs (cDMARD) such as methotrexate together with low‐dose glucocorticoids could be the “new gold standard” for early RA treatment. Considering that, on the one hand, current evidence‐based guidelines recommend that patients must fail cDMARD before applying biologic DMARD in RA management, and, on the other hand, there is strong evidence of the success of biologics in patients with moderate to severe RA, this question needs to be carefully discussed.…”

mentioning

confidence: 99%

Inflammation: Treatment Progress and Limitations

Cascorbi

2017

Clin Pharma and Therapeutics

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There is an increasing understanding on the etiology of chronic immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, or rheumatoid arthritis. Large consortia contributed to the elucidation of the genetics, for instance, of IBD identifying a number of genes involved in innate mucosal defense and immune tolerance (most prominent, e.g., NOD2) and other related processes. For a number of such diseases, common genetic susceptibility loci were identified, suggesting overlapping immune response pathways, although there is no causality of single genetic traits. In particular, the elucidation of main triggers of inflammation like tumor necrosis factor alpha (TNFα), integrins, specific cytokines like interleukin (IL)-6 or IL-23 launched the successful development of new pharmacological approaches, leading to a tremendous improvement of therapeutic outcomes.

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Is There a Renaissance of Glucocorticoids in Rheumatoid Arthritis?

Cited by 8 publications

References 4 publications

Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

Modeling Corticosteroid Pharmacogenomics and Proteomics in Rat Liver

Inflammation: Treatment Progress and Limitations

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