Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2013
Randomized Controlled Trial Multicenter StudyA phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis.
The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA). ⋯ Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA.
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Arthritis Res. Ther. · Jan 2013
Randomized Controlled Trial Multicenter StudySafety, tolerability, pharmacokinetics and pharmacodynamics of an anti- oncostatin M monoclonal antibody in rheumatoid arthritis: results from phase II randomized, placebo-controlled trials.
Oncostatin M (OSM) has been implicated in the pathophysiology of rheumatoid arthritis (RA) through its effect on inflammation and joint damage. GSK315234 is a humanised anti-OSM Immunoglobulin G1 (IgG1) monoclonal antibody (mAb). This 3-part study examines the safety, tolerability and efficacy of GSK315234 in patients with active RA. ⋯ Our data highlighted the importance of binding affinity and off-rate effect of a mAb to fully neutralize the target and how this may influence its efficacy and potentially worsen disease activity. Using an anti-OSM mAb with high affinity should test this hypothesis and examine the potential of OSM as a therapeutic target in RA.
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Arthritis Res. Ther. · Jan 2013
Hyaluronic acid fragments enhance the inflammatory and catabolic response in human intervertebral disc cells through modulation of toll-like receptor 2 signalling pathways.
Intervertebral disc (IVD) degeneration is characterized by extracellular matrix breakdown and is considered to be a primary cause of discogenic back pain. Although increases in pro-inflammatory cytokine levels within degenerating discs are associated with discogenic back pain, the mechanisms leading to their overproduction have not yet been elucidated. As fragmentation of matrix components occurs during IVD degeneration, we assessed the potential involvement of hyaluronic acid fragments (fHAs) in the induction of inflammatory and catabolic mediators. ⋯ These findings suggest that fHAs may have the potential to mediate IVD degeneration and discogenic back pain through activation of the TLR2 signaling pathway in resident IVD cells.
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Arthritis Res. Ther. · Jan 2013
The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study.
Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH. ⋯ The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies.
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Arthritis Res. Ther. · Jan 2013
Randomized Controlled Trial Multicenter StudyLong-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.
The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. ⋯ The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use.