Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study

<p>Abstract</p> <p>Background</p> <p>Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate.</p> <p>Methods</p> <p>Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks.</p> <p>Results</p> <p>Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred.</p> <p>Conclusion</p> <p>The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate.</p> <p>Trial Registration</p> <p>(ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00784628">NCT00784628</a>)</p

The FunGenES Database: A Genomics Resource for Mouse Embryonic Stem Cell Differentiation

Embryonic stem (ES) cells have high self-renewal capacity and the potential to differentiate into a large variety of cell types. To investigate gene networks operating in pluripotent ES cells and their derivatives, the “Functional Genomics in Embryonic Stem Cells” consortium (FunGenES) has analyzed the transcriptome of mouse ES cells in eleven diverse settings representing sixty-seven experimental conditions. To better illustrate gene expression profiles in mouse ES cells, we have organized the results in an interactive database with a number of features and tools. Specifically, we have generated clusters of transcripts that behave the same way under the entire spectrum of the sixty-seven experimental conditions; we have assembled genes in groups according to their time of expression during successive days of ES cell differentiation; we have included expression profiles of specific gene classes such as transcription regulatory factors and Expressed Sequence Tags; transcripts have been arranged in “Expression Waves” and juxtaposed to genes with opposite or complementary expression patterns; we have designed search engines to display the expression profile of any transcript during ES cell differentiation; gene expression data have been organized in animated graphs of KEGG signaling and metabolic pathways; and finally, we have incorporated advanced functional annotations for individual genes or gene clusters of interest and links to microarray and genomic resources. The FunGenES database provides a comprehensive resource for studies into the biology of ES cells

Effect of risk factors on complicated and uncomplicated ulcers in the TARGET lumiracoxib outcomes study

BACKGROUND ; AIMS: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups. METHODS: Patients with osteoarthritis (age, >or=50 y) were randomized to receive lumiracoxib 400 mg once daily, naproxen 500 mg twice daily, or ibuprofen 800 mg 3 times daily for 12 months. Events were categorized by a blinded adjudication committee. The primary end point was all definite or probable ulcer complications. RESULTS: For patients taking NSAIDs, factors associated with an increased risk of ulcer complications were age 65 years or older (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.48-3.59), previous history of gastrointestinal bleed or ulcer (HR, 3.61; 95% CI, 1.86-7.00), non-Caucasian racial origin (HR, 2.10; 95% CI, 1.35-3.27), and male sex (HR, 1.70; 95% CI, 1.08-2.68). With lumiracoxib, significant risk factors were age 65 years or older (HR, 3.18; 95% CI, 1.40-7.20), male sex (HR, 2.60; 95% CI, 1.25-5.40), non-Caucasian racial origin (HR, 2.16; 95% CI, 1.02-4.59), and concomitant aspirin use (HR, 2.89; 95% CI, 1.40-5.97). Increased risks in patients age 65 years and older were increased further if other risk factors were present. Lumiracoxib maintained an advantage over NSAIDs across all subgroups except aspirin use. CONCLUSIONS: Lumiracoxib was associated with a reduced risk of ulcer complications compared with NSAIDs in all significant subgroups except aspirin users

Fresh frozen bone in oral and maxillofacial surgery

The aim of the current study was to review the use of fresh frozen bone (FFB) in oral and maxillofacial surgery. We performed a review of the articles published in the literature between 1976 and May 2014 analyzing three medical databases (PubMed, Cochrane Library, and Embase) and using specific search terms. Literature analysis on FEB applications in oral and maxillofacial surgery revealed 47 articles between 1976 and May 2014. There are 46 clinical articles and one review. Clinical articles are represented by 22 case reports and case series and 24 retrospective studies. Classifying the scientific production by year of publication, it is evident that especially during the last 6 years there was an increase of FEB graft use in oral and maxillofacial approaches. The literature analysis on FFB's use shows that its application in oral and maxillofacial surgery began slowly in 1992 with Perrott and since 2006 it had a real development. The recent significant increase emphasizes the importance of FFB for bone regeneration in oral and maxillofacial surgery. This review found consistent evidence of FFB's use increase in oral and maxillofacial surgery suggesting a valid instrument for bone regeneration. To date, risks connected to the infections' transmission and to the immunogenic potential are extremely low and could be considered practically absent. So, this is an important alternative in the preimplant reconstructive surgery

GRAVITY: a four-telescope beam combiner instrument for the VLTI

International audienc

Bringing the New Adaptive Optics Module for Interferometry (NAOMI) into Operation

published in the ESO Messenge