Seminars in arthritis and rheumatism
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Semin. Arthritis Rheum. · Jun 2020
Randomized Controlled Trial Multicenter StudyThe impact of a disease flare during tapering of DMARDs on the lives of rheumatoid arthritis patients.
To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment. ⋯ A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients.
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Urate is the end-product of the purine metabolism in humans. The dominant source of urate is endogenous purines and the remainder comes through diet. Approximately two thirds of urate is eliminated via the kidney with the rest excreted in the feces. ⋯ Hyperuricemia can result in the formation of monosodium urate (MSU) crystals that may be recognized as danger signals by the immune system. This immune response results in the activation of the NLRP3 inflammasome and ultimately in the production and release of interleukin-1β, and IL-18, that mediate both inflammation, pyroptotic cell death, and necroinflammation. It has also been demonstrated that soluble urate mediates effects on the kidney to induce hypertension and can induce long term epigenetic reprogramming in myeloid cells to induce "trained immunity." Together, these sequelae of urate are thought to mediate most of the physiological effects of hyperuricemia and gout, illustrating this biologically active molecule is more than just an "end-product" of purine metabolism.
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Semin. Arthritis Rheum. · Jun 2020
Randomized Controlled TrialOnset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study.
To examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773). ⋯ Subcutaneous tanezumab provided statistically significant improvements compared with placebo in average daily index joint pain within the first week and WOMAC Pain and Physical Function (week 2) that were generally maintained throughout the 16-week treatment period. Tanezumab 5 mg provided only modest additional efficacy over tanezumab 2.5 mg.