Increased pretreatment serum IFN-ß/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.

OBJECTIVE: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. METHODS: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-ß activity were measured using a functional reporter cell assay. RESULTS: In the test set, an increased ratio of IFN-ß to IFN-α (IFN-ß/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-ß/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-ß/α activity ratio (p=0.005). CONCLUSIONS: Increased pretreatment serum IFN-ß/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.

Efficient dynamic replication algorithm using agent for data grid.

In data grids scientific and business applications produce huge volume of data which needs to be transferred among the distributed and heterogeneous nodes of data grids. Data replication provides a solution for managing data files efficiently in large grids. The data replication helps in enhancing the data availability which reduces the overall access time of the file. In this paper an algorithm, namely, EDRA using agents for data grid, has been proposed and implemented. EDRA consists of dynamic replication of hierarchical structure taken into account for the selection of best replica. Decision for selecting the best replica is based on scheduling parameters. The scheduling parameters are bandwidth, load gauge, and computing capacity of the node. The scheduling in data grid helps in reducing the data access time. The distribution of the load on the nodes of data grid is done evenly by considering scheduling parameters. EDRA is implemented using data grid simulator, namely, OptorSim. European Data Grid CMS test bed topology is used in this experiment. The simulation results are obtained by comparing BHR, LRU, No Replication, and EDRA. The result shows the efficiency of EDRA algorithm in terms of mean job execution time, network usage, and storage usage of node.

Not all TNF inhibitors in rheumatoid arthritis are created equal: important clinical differences.

INTRODUCTION: Anti-TNF therapy has dramatically changed how we manage rheumatoid arthritis. There are many similarities among the five approved agents but also some important differences. Rheumatologists have 5 different options to choose from when they are ready to commence anti-TNF therapy. Although all block the TNF cytokine, there are important critical differences among them that affect their safety profile and clinical utility in certain scenarios. Unfortunately, there are no head to head trials to compare the different anti-TNF agents and none appear to be in the horizon. Areas covered: This article reviews the various clinical situations where it may be important to use a particular anti-TNF agent. The authors also give their expert opinion and future perspectives on the area. Expert opinion: Although there are many similarities among the five different TNFi that are clinically available, there are important clinical niches, where the limited data that are available, that clearly support the preferential use of a particular agent or class of agents. Assays or tests that allow us to find the 'sweet spot' of TNF inhibition at the level of each patient are long overdue.

Toxoplasma Infection in an Immunocompetent Host: Possible Risk of Living with Multiple Cats.

A 32-year-old man presented with agitation, headache, and confusion. He was immunocompetent and had been living with multiple cats for many years. His vital signs were stable. He was afebrile. Multiple blood tests did not show any serious problem. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing white matter lesions. Cerebrospinal fluid analysis did not show any signs of infection. Based on a presumptive diagnosis of multiple sclerosis, high-dose corticosteroid treatment was started. However, this caused worsening of the symptoms and increased the size of the lesions. Corticosteroids were discontinued and biopsy was done. Biopsy of the lesions confirmed Toxoplasma gondii infection, and treatment with pyrimethamine/sulfadiazine was initiated. Treatment decreased the size of the lesions dramatically. Toxoplasma infection of the central nervous system (CNS) is rare in immunocompetent hosts. Living with multiple cats is believed to be a risk factor for Toxoplasma infection in immunocompetent hosts.

Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials.

OBJECTIVE: Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs. METHODS: Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure. RESULTS: The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4-7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date. CONCLUSION: The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies.

How far you can trust c-ANCA?

The suspicion of a serious condition arises if a smoker is coughing and losing weight constantly. Serology and imaging are great options for diagnosis, but what is their specificity? A 62-year-old man presented with persistent cough, weight loss and hypoxia. A chest x-ray revealed bilateral interstitial infiltrates. Treatment with several antibiotics failed. Serological results showed antineutrophil cytoplasmic antibodies (c-ANCA) positivity. However, biopsy result indicated cryptogenic organising pneumonia. This case report discloses the differential diagnosis of c-ANCA positive interstitial lung disease in detail.

Omalizumab for treatment of allergic rhinitis.

INTRODUCTION: Immunoglobulin E (IgE) is a key pathogenic factor of allergic rhinitis, a prevalent disease adversely affecting quality of life and productivity. AREAS COVERED: Binding of inhaled allergens to IgE on the surface of basophils and mast cells, with subsequent cross-linkage of IgE and aggregation of high-affinity receptors for IgE (FcϵRI), triggers the release of inflammatory mediators, followed by the onset of allergic rhinitis symptoms. Current therapeutic strategies include corticosteroids, mast cell stabilizers, leukotriene receptor antagonists, anticholinergics, antihistamines and allergen immunotherapy. Removal of circulating free IgE by the recombinant humanized monoclonal anti-IgE antibody, omalizumab (Xolair), represents a novel therapeutic approach. Omalizumab selectively binds to the Cϵ3 domain of IgE at the site of FcϵR1 binding, thus blocking binding of IgE to effector cells. We review omalizumab's clinical efficacy, administration, use with immunotherapy and safety in allergic rhinitis. EXPERT OPINION: Omalizumab may provide a new treatment strategy for allergic rhinitis. The high cost of omalizumab precludes its chronic use for allergic rhinitis and it is not FDA approved for this indication; however, its periodic use may be justified in treatment resistant patients, especially those with seasonal disease.