Sulphasalazine: Mechanism of Action in Rheumatoid Arthritis

Smedegård, G.; Björk, Jakob

doi:10.1093/rheumatology/xxxiv.suppl_2.7

Cited by 74 publications

(33 citation statements)

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“…Finally, our results rule out the notion of an increased risk of pneumonia associated with sulfasalazine (HR 0.7 [95% CI 0.5-1.0]). This marginally significant effect may or may not relate to sulfasalazine's known mechanisms of action (53,54). Although observational studies reflect actual clinical practice in the community, nonrandom assignment to therapy can confound the association between treatment and pneumonia unless all important covariates are controlled for.…”

Section: Discussionmentioning

confidence: 99%

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

Wolfe¹,

Caplan²,

Michaud³

2006

Arthritis & Rheumatism

423

233

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Objective. Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk.Methods. RA patients (n ‫؍‬ 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments.Results Conclusion. There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.

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Section: Discussionmentioning

confidence: 99%

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

Wolfe¹,

Caplan²,

Michaud³

2006

Arthritis & Rheumatism

423

233

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“…SSZ, a conjugate of 5-aminosalicylic acid (5-ASA) and sulphapyridine, is used in the treatment of RA and inflammatory bowel disease [2,12,13]. Many patients with RA need second-line drugs, but few continue to take them for the long periods necessary to make a significant impact on the disease [5].…”

Section: Discussionmentioning

confidence: 99%

Seizures and hepatotoxicity following sulphasalazine administration

Şentürk

Aydintug

Düzgün

et al. 1997

Rheumatology International

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Sulphasalazine (SSZ) is a widely used second-line agent for several rheumatic diseases. Most of its side effects are relatively minor and dose dependent. We report a patient with juvenile onset chronic arthritis who developed hepatotoxicity and seizures on the third week of SSZ when the daily dose was increased to 2 g. Clinical and laboratory findings of liver and central nervous system toxicity gradually returned to normal in the month following SSZ withdrawal.

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“…Cells were seeded at an initial density of 3 ϫ 10 5 /ml and were exposed to SSZ for a period of 3 months to mimic the slow action of SSZ, which achieves its optimal activity after a period of 6 to 12 weeks (Brooks, 2001). Since peak plasma levels of RA patients receiving a daily dose of 2 to 3 g of SSZ can reach levels of 1 mM, whereas steady-state plasma levels of SSZ can reach 0.1 mM (Baggott et al, 1992;Smedegard and Bjork, 1995), we exposed cells to intermediate concentrations of 0.4 to 0.6 mM SSZ, which caused a moderate antiproliferative effect (IC 50 -IC 75 ) in previously unexposed cells. Cell cultures were refreshed twice weekly.…”

Section: Methodsmentioning

confidence: 99%

Sulfasalazine Down-Regulates the Expression of the Angiogenic Factors Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase and Interleukin-8 in Human Monocytic-Macrophage THP1 and U937 Cells

Bruin¹,

Peters²,

Oerlemans³

et al. 2004

Mol Pharmacol

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Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and interleukin-8 (IL-8) are angiogenic factors produced by tumor infiltrating macrophages. Here, we show that prolonged exposure of human monocytic/macrophage THP1 and U937 cells to sulfasalazine, an anti-inflammatory drug and inhibitor of nuclear factor-B (NF-B), resulted in down-regulation of PD-ECGF/TP and IL-8 (mRNA, protein and activity) along with elimination of their induction by tumor necrosis factor-␣ and interferon-␥. Concomitantly, sulfasalazineexposed cells were markedly resistant to 5Ј-deoxyfluorouridine, the last intermediate of capecitabine requiring activation by PD-ECGF/TP. This is the first report suggesting that disruption of NF-B-dependent signaling pathways can provoke a marked and sustained down-regulation of macrophage-related angiogenic factors. However, this may also negatively affect capecitabine efficacy.

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Sulphasalazine: Mechanism of Action in Rheumatoid Arthritis

Cited by 74 publications

References 0 publications

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

Seizures and hepatotoxicity following sulphasalazine administration

Sulfasalazine Down-Regulates the Expression of the Angiogenic Factors Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase and Interleukin-8 in Human Monocytic-Macrophage THP1 and U937 Cells

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