Arthritis research & therapy
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Arthritis Res. Ther. · Sep 2013
Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).
Eosinophilic granulomatosis with polyangiitis (EGPA) is part of antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of EGPA patients are ANCA-positive, suggesting a role for B cells in the pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be effective in ANCA-positive EGPA, but very few patients have been published to date. The role of RTX in the treatment of ANCA-negative EGPA is unclear. ⋯ In our analysis on nine patients with EGPA resistant to standard therapy, rituximab proved to be an efficient and safe treatment for ANCA-positive and ANCA-negative patients. Preemptive retreatment with RTX, combined with standard maintenance immunosuppressants, resulted in a sustained treatment response. Prospective, randomized trials evaluating the use of RTX in EGPA are warranted.
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Arthritis Res. Ther. · Feb 2013
Randomized Controlled Trial Clinical TrialExercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?
Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. ⋯ Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects.
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Arthritis Res. Ther. · Feb 2013
Editorial CommentTo target or not to target APRIL in systemic lupus erythematosus: that is the question!
Among the cytokines that regulate B-cell homeostasis are the TNF-like ligands B-lymphocyte stimulator (BLyS; also B-cell activation factor) and a proliferation-inducing ligand (APRIL). BLyS and APRIL share two receptors; that is, B-cell maturation antigen and transmembrane activator and CAML interactor. ⋯ One previously approved drug is belimumab, which antagonizes the B-cell stimulator BLyS. Atacicept, another biologic inhibiting BLyS and APRIL, was terminated for serious adverse events--raising the question of whether APRIL should be neutralized in autoimmune diseases.
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Arthritis Res. Ther. · Feb 2013
Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes.
This study investigated whether the calcineurin inhibitor, tacrolimus, suppresses receptor activator of NF-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLS) through regulation of IL-6/Janus activated kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS3) signaling. ⋯ These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3.
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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.