Arthritis research & therapy
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Arthritis Res. Ther. · Nov 2016
Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout.
Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models. ⋯ Our studies reveal that IL-37 limits runaway inflammation initiated by MSU crystal-induced immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both preventive and therapeutic effects in gouty arthritis.
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Arthritis Res. Ther. · Nov 2016
Multicenter Study Comparative Study Observational StudyComparative effectiveness of treatment with the first TNF antagonist in monotherapy, the first TNF antagonist plus one conventional synthetic disease-modifying antirheumatic drug, and the first TNF antagonist plus two or more conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus, they are treated with the first TNF antagonists in monotherapy. The aim of this study was to analyse the csDMARD and GC prescription patterns before and during treatment with the first TNF antagonist, and compare their effectiveness in three groups of patients. ⋯ The three groups of patiernts, have different comorbidities and disease characteristics. Treatment with low or very low doses of GCs is common. True monotherapy with the first TNF antagonist without prednisone or csDMARDs is infrequent. After controlling for potential confounders, effectiveness was a little different.
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Arthritis Res. Ther. · Nov 2016
Randomized Controlled Trial Multicenter StudyChondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study.
In osteoarthritis (OA) treatment, although chondroitin sulfate (CS) was found in a number of studies using radiography to have a structure-modifying effect, to date CS use is still under debate. A clinical study using quantitative magnetic resonance imaging (qMRI) is therefore of the utmost importance. Here we report data from a 24-month, randomised, double-blind, double-dummy, controlled, comparative exploratory study of knee OA. The primary endpoint was to determine the effect of CS 1200 mg/day versus celecoxib 200 mg/day on cartilage volume loss (CVL) in the lateral compartment over time as measured by qMRI. Secondary endpoints included assessment of the OA structural changes and signs and symptoms of OA. ⋯ This study demonstrated, for the first time in a 2-year randomised controlled trial using qMRI, the superiority of CS over celecoxib at reducing CVL in knee OA patients.
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Arthritis Res. Ther. · Oct 2016
Randomized Controlled TrialSarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY.
Interleukin 6 (IL-6) signaling plays a key role in the pathophysiology of rheumatoid arthritis (RA) and is inhibited by sarilumab, a human monoclonal antibody blocking the IL-6 receptor alpha (IL-6Rα). The effects of sarilumab plus methotrexate (MTX) on serum biomarkers of joint damage and bone resorption were assessed in two independent studies (phase II (part A) and phase III (part B)) of patients with RA with a history of inadequate response to MTX from the MOBILITY study (NCT01061736). ⋯ Sarilumab plus MTX significantly suppressed biomarkers of bone resorption and joint damage, as compared with placebo plus MTX, in patients with RA. Additional work is needed to determine whether differences in biomarker profiles at baseline or posttreatment can identify patients who achieve improvement in disease activity.
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Arthritis Res. Ther. · Sep 2016
Randomized Controlled TrialSarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial.
Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT. ⋯ In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab.