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Dougados M.,University of Paris Descartes | Braun J.,Rheumazentrum Ruhrgebiet | Szanto S.,Debrecen University | Combe B.,Montpellier University | And 3 more authors.
Rheumatology (United Kingdom) | Year: 2012

Objective. To evaluate the longer-term efficacy of etanercept in patients with severe and advanced active AS.Methods. Seventy-seven patients who completed the randomized, double-blind, placebo-controlled 12-week SPINE study enrolled in a 12-week open-label extension and received s.c. etanercept 50 mg once weekly. The etanercept/etanercept group received a total of 24 weeks treatment with etanercept (n = 38); the placebo/etanercept group received placebo during the double-blind study then 12 weeks' etanercept treatment during the open-label extension (n = 39).Results. At the end of the open-label extension, BASDAI scores in the etanercept/etanercept group had further decreased beyond reductions observed during the double-blind study [mean (s.d.) change from baseline -37.6 (22.4) at end of extension vs -27.4 (23.8) at end of double-blind study]. Mean (s.d.) BASDAI scores also improved in the placebo/etanercept group once switched to etanercept [-28.6 (24.3) vs -15.0 (20.0)]. Similar trends were observed in BASFI and BASMI scores. In the placebo/etanercept group, total back pain decreased to similar levels achieved in the etanercept group in the double-blind study. Pain levels continued to decrease with longer-term etanercept therapy in the etanercept/etanercept group.Conclusion. Despite the improvements in symptoms and inflammatory markers observed shortly after initiation of once-weekly etanercept, there was no notable plateauing effect on patient-reported outcomes. Indeed, signs and symptoms of severe and advanced active AS continued to improve after up to 24 weeks, treatment with etanercept. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Source

Meszaros T.,Semmelweis University | Fust G.,Semmelweis University | Farkas H.,Semmelweis University | Jakab L.,Semmelweis University | And 11 more authors.
Lupus | Year: 2010

The presence of anti-C1-inhibitor (anti-C1-INH) autoantibodies is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence, diagnostic value, and/or significance in systemic lupus erythematosus (SLE). In a multicentre study, we determined the levels of autoantibodies to C1-inhibitor in sera from 202 patients with SLE and 134 healthy controls. Additional clinical and laboratory parameters, such as organ involvement, as well as anti-C1q, anti-double-stranded DNA antibody, erythrocyte sedimentation rate, C-reactive protein, C3 and C4 serum complement levels have been studied in patients. The level of anti-C1-INH IgG was significantly higher (p = 0.034) in SLE patients, than in the controls. A high anti-C1-INH level of ĝ‰¥0.4 U/ml (mean of controls + 2 SD) was found in 17% of the patients, but in only 4% of the controls (p = 0.0003). The SLEDAI score was significantly higher (p = 0.048) and the duration of SLE was significantly longer (p = 0.0004) among patients with elevated anti-C1-INH levels compared with patients without this autoantibody (median disease duration 8 vs. 17 years, respectively). Anti-C1-INH level was not correlated with any other laboratory parameter or organ manifestation of the disease. These findings indicate that the anti-C1-INH level is higher in SLE patients than in healthy controls and furthermore, the anti-C1-INH level correlates with the duration and activity of the disease. © The Author(s), 2010. Source

Buzas E.I.,Semmelweis University | Gyorgy B.,Semmelweis University | Nagy G.,Polyclinic of the Hospitaller Brothers of St. John of God | Falus A.,Semmelweis University | Gay S.,University of Zurich
Nature Reviews Rheumatology | Year: 2014

The discovery that submicron-sized extracellular vesicles (EVs) are generated by both prokaryotic and eukaryotic cells might have a profound effect on experimental and clinical sciences, and could pave the way for new strategies to combat various diseases. EVs are carriers of pathogen-associated and damage-associated molecular patterns, cytokines, autoantigens and tissue-degrading enzymes. In addition to a possible role in the pathogenesis of a number of inflammatory conditions, such as infections and autoimmune diseases, EVs, including microvesicles (also known as microparticles), exosomes and apoptotic vesicles, have therapeutic potential and might be used as biomarkers for inflammatory diseases. Therefore, molecular diagnostics and targeted therapy could benefit from expanding knowledge in the field. In this Review, we summarize important developments and propose that extracellular vesicles could be used as therapeutic vehicles and as targets for the treatment and prevention of inflammatory diseases. © 2014 Macmillan Publishers Limited. Source

Szili D.,Eotvos Lorand University | Cserhalmi M.,Eotvos Lorand University | Banko Z.,Eotvos Lorand University | Nagy G.,Polyclinic of the Hospitaller Brothers of St. John of God | And 2 more authors.
mAbs | Year: 2014

The Fc receptor (FcγRIIb) inhibits B cell responses when coengaged with B cell receptor (BCR), and has become a target for new autoimmune disease therapeutics. For example, BCR and FcγRIIb coengagement via the Fc-engineered anti-CD19 XmAb5871 suppresses humoral immune responses. We now assess effects of XmAb5871 on other activation pathways, including the pathogen-associated molecular pattern receptor, TLR9. Since TLR9 signaling is implicated in autoimmune diseases, we asked if XmAb5871 could inhibit TLR9 costimulation. We show that XmAb5871 decreases ERK and AKT activation, cell proliferation, cytokine, and IgG production induced by BCR and/or TLR9 signals. XmAb5871 also inhibited differentiation of citrullinated peptide-specific plasma cells from rheumatoid arthritis patients. XmAb5871 may therefore have potential to suppress pathogenic B cells in autoimmune diseases. © 2014 Landes Bioscience. Source

Dougados M.,University of Paris Descartes | Braun J.,Rheumazentrum Ruhrgebiet | Szanto S.,Debrecen University | Combe B.,Lapeyronie hospital | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: Patients with advanced ankylosing spondylitis (AS) experience disability because of reduced spinal mobility and pulmonary function impairment. This placebo-controlled study evaluated the effect of etanercept (ETN) in patients with advanced AS. Methods: A multicentre randomised double-blind placebo-controlled trial of 12 weeks' duration was performed. Patients had definite (modified New York criteria), active (Bath AS Disease Activity Index (BASDAI) ≥40), severe (radiological intervertebral bridges) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive. They were treated with ETN 50 mg once weekly or identical placebo (PBO). Results: Of the 95 patients screened, 82 were randomised to receive ETN (n=39) or PBO (n=43). At baseline the disease was active (mean BASDAI 61.0±13.4, C reactive protein (CRP) 20.7±25.5 mg/l) and severe (mean Bath AS Metrology Index (BASMI) 5.7±1.3, mSASSS 36.5±20.5);forced pulmonary vital capacity (FVC) was 3.3±0.7 l. Improvement in BASDAI (normalised net incremental area under the curve between baseline and week 12, primary end point) was significantly greater in the ETN group than in the PBO group (-19.8±16.5 vs-11.0±16.4, p=0.019). Moreover, at week 12, ETN gave better results than PBO for the BASDAI (-26.4±19.7 vs -14.4±19.7;p=0.008), total back pain (-29.2±24.0 vs-14.9±24.0;p=0.010), BASFI (-21.7±17.6 vs-10.1±17.6;p=0. 004), BASMI (-0.6±0.6 vs -0.2±0.6;p=0.011), CRP level (-15.7±14.2 vs -1.3±14.2;p<0.001) and FVC (+160±280 ml vs -20±280 ml;p=0.006). Conclusions: ETN has short-term efficacy for patients with advanced AS, as was previously reported for less advanced disease. The efficacy is observed for the main symptoms (pain) and on markers of inflammation (CRP), as well as disease severity in terms of spinal mobility and pulmonary function. Source

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