Rheumatoid Arthritis

Mehta, Nimish; Schneider, Lynne Kolton; McCardell, Emilie

doi:10.1097/rhu.0000000000000410

Cited by 5 publications

(1 citation statement)

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“…24 However, rheumatologists preferred to prescribe combination therapy rather than monotherapy because of the increased efficacy and enhanced improvement of the patient over time. 5 Dell et al performed a two years study and measured the difference in the improvement of patients with three different treatments i.e, Methotrexate (MXT) alone, Sulfasalazine (SFS) and Hydroxychloroquine (HCQ) combined treatment and combination of all three. The combined treatment of MXT, SFS and HCQ, called triple therapy is found to be an effective treatment that increases efficacy without an increase in the toxicity when compared to gold standard treatment of MXT alone.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Simultaneous Bioanalytical Method for Methotrexate, Sulfasalazine and Hydroxychloroquine in Rat Plasma following Single Step Protein Precipitation Technique

Reddy¹,

Sahu²,

Sharma³

et al. 2020

IJPER

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Background: Triple therapy of methotrexate, sulfasalazine and hydroxychloroquine is widely used in the treatment of rheumatoid arthritis. Different studies reported the superior efficacy of combination of these three drugs in the improvement of this disease state. However, there is still a lot of scopes remains for preclinical study of this combination in future. Establishment of bioanalytical method is essential for quantitating these analytes in the samples from such types of studies. Therefore, in this study, we aim to develop a simultaneous method for quantification of methotrexate, sulfasalazine and hydroxychloroquine in rat plasma through a single run. Materials and Methods: The method includes a simple single step protein precipitation technique for extraction of all the three analytes from rat plasma with more than 84% recovery. The method was validated according to the USFDA guideline for a calibration range of 0.50-10μg/mL. Results: Overall, the method showed acceptable accuracy (92.14-116.12%) and precision (%coefficient of variation; 0.79-11.94%) at lower limit of quantification and three quality control levels. Analytes were found to be stable in all the tested stability study conditions. Conclusion: We have established a simultaneous bioanalytical method for methotrexate, sulfasalazine and hydroxychloroquine in rat plasma. Applicability of the method has been established through an oral pharmacokinetic study of the combination in rat.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a Simultaneous Bioanalytical Method for Methotrexate, Sulfasalazine and Hydroxychloroquine in Rat Plasma following Single Step Protein Precipitation Technique

Reddy¹,

Sahu²,

Sharma³

et al. 2020

IJPER

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Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases

et al. 2018

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ObjectiveThese analyses aim to comparatively evaluate the persistence on treatment of different biological disease-modifying antirheumatic drugs (bDMARDs) when administered in monotherapy compared with combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA) patients receiving first-line biologics.DesignThis is a retrospective observational study on Administrative Healthcare Databases.MethodsData were extracted from healthcare databases of the Lombardy Region, Italy (2004–2013), as a part of the RECord-linkage On Rheumatic Diseases study, on behalf of the Italian Society for Rheumatology. Analyses included patients with RA starting first-line approved course of bDMARDs and evaluated drug survival by using Cox proportional hazard models. Results are presented as HRs and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease duration, Charlson Comorbidity Index (CCI), previous infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).Results4478 patients with RA were included (17.84% monotherapy). Etanercept, adalimumab and infliximab were the most prescribed first-line biologics. bDMARD monotherapy was associated with longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the risk of bDMARD withdrawal.ConclusionAdalimumab and infliximab monotherapies show lower retention rate compared with etanercept. The relatively small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors makes more difficult to achieve conclusive results with other biologics. Concomitant methotrexate, leflunomide and csDMARDs combination associate with longer survival on bDMARD. Our data confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

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Mechanism of Mir-218-5P in Autophagy, Apoptosis and Oxidative Stress in Rheumatoid Arthritis Synovial Fibroblasts is Mediated by Klf9 and Jak/Stat3 Pathways

Chen

Zhang

et al. 2021

Journal of Investigative Medicine

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This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

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Rheumatoid Arthritis

Cited by 5 publications

References 0 publications

Development and Validation of a Simultaneous Bioanalytical Method for Methotrexate, Sulfasalazine and Hydroxychloroquine in Rat Plasma following Single Step Protein Precipitation Technique

Development and Validation of a Simultaneous Bioanalytical Method for Methotrexate, Sulfasalazine and Hydroxychloroquine in Rat Plasma following Single Step Protein Precipitation Technique

Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases

Mechanism of Mir-218-5P in Autophagy, Apoptosis and Oxidative Stress in Rheumatoid Arthritis Synovial Fibroblasts is Mediated by Klf9 and Jak/Stat3 Pathways

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