Lupus (SLE)
67 views | +0 today
Follow
Your new post is loading...
Your new post is loading...
Scooped by innovIDrsrchr
Scoop.it!

Affordable Care Act & Systemic Lupus (SLE) - TheLupusChannel.com

Affordable Care Act & Systemic Lupus (SLE) - TheLupusChannel.com | Lupus (SLE) | Scoop.it
For many years my family struggled with trying to find insurance companies who would insure us with a reasonable premium. The Affordable Care Act saved us.
more...
No comment yet.
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Preclinical Systemic Lupus Erythematosus

Preclinical lupus encompasses a spectrum from enhanced SLE risk without clinical symptoms to individuals with autoantibodies and some SLE clinical features without meeting ACR classification. Studies have identified antibody and serological biomarkers years before disease onset. Incomplete lupus and undifferentiated connective tissue disease may occur during preclinical disease periods, but only 10–20% of these individuals transition to SLE and many have a mild disease course. Further studies are warranted to characterize biomarkers of early disease, identify individuals in need of close monitoring or preventive interventions, and elucidate mechanisms of disease pathogenesis without confounding factors of immunosuppressive medications or organ damage.


Via Krishan Maggon
innovIDrsrchr's insight:

Bio markers have been elusive in SLE.

more...
Krishan Maggon 's curator insight, October 28, 2014 3:05 AM
Rheumatic Disease Clinics of North America

Volume 40, Issue 4, November 2014, Pages 621–635

Preclinical Rheumatic Disease

 Preclinical Systemic Lupus Erythematosus Julie M. Robertson, PhDa, Judith A. James, MD, PhDa, b, c, d, ,   DOI: 10.1016/j.rdc.2014.07.004
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

The role of T cells in systemic lupus erythematosus: an update : Current Opinion in Rheumatology

The role of T cells in systemic lupus erythematosus: an update : Current Opinion in Rheumatology | Lupus (SLE) | Scoop.it
Purpose of reviewTo describe our current understanding of the role of T cells in the pathophysiology of systemic lupus erythematosus (SLE).
Recent findingsOver the last few years, the dominant role of T cells in autoimmunity and SLE was established. Genome-wide-association studies led to the dis...

Via Krishan Maggon
more...
No comment yet.
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Lilly to Discontinue Development of Tabalumab Based on Failed Efficacy Results in Phase 3 Lupus Studies

Lilly to Discontinue Development of Tabalumab Based on Failed Efficacy Results in Phase 3 Lupus Studies | Lupus (SLE) | Scoop.it

Eli Lilly and Company (NYSE: LLY)  announced today it will discontinue development of tabalumab­ -- being studied for the treatment of systemic lupus erythematosus (SLE, commonly known as lupus) -- due to insufficient efficacy in two pivotal Phase 3 trials. The decision was not based on safety concerns. ­­­­

In the ILLUMINATE 1 study, tabalumab did not achieve the primary endpoint, at either dose studied, of statistically significant improvement on SRI-5 (SLE Responder Index-5, a measurement of lupus disease activity and response), compared to standard of care therapy. In ILLUMINATE 2, the higher dose of tabalumab met this endpoint, the first time a lupus study has achieved this efficacy measure as a primary endpoint in a Phase 3 trial. Collectively, the data from these studies did not meet expectations for efficacy in the context of existing treatments. The overall safety profile showed a similar frequency of adverse events in patients treated with either tabalumab or standard of care. Lilly intends to submit these data for disclosure in appropriate upcoming scientific venues.

Given the overall efficacy results from these two pivotal Phase 3 studies, Lilly will not move forward with submissions to global regulators. Lilly will work with investigators to appropriately conclude these studies in the interest of patient safety.

 

The decision to discontinue development of tabalumab for lupus is expected to result in a third-quarter charge to research and development expense of up to $75 million (pretax), or approximately $0.04 - $0.05 per share (after-tax).


Via Krishan Maggon
more...
No comment yet.
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype

DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype | Lupus (SLE) | Scoop.it

Highlights

 

We characterized the DNA methylome and the transcriptome in CD4+ T cells of SLE.

Integrated analysis of our data highlights the epigenetic mechanism in SLE.

The specific DNA methylation changes are correlated with clinical phenotype of SLE.


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, October 30, 2014 4:30 AM
Journal of Autoimmunity

Volume 54, November 2014, Pages 127–136

Honoring the contributions of Ruth Arnon and Michael Sela

 DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotypeMing Zhaoa, 1, Siyang Liub, 1, Shuangyan Luoa, Honglong Wub, Meini Tanga, Wenjing Chenga, Qing Zhanga, Peng Zhanga, Xinhai Yua, Yudong Xiab, Na Yib, Fei Gaob, Li Wangb, Susan Yungc, Tak Mao Chanc, Amr H. Sawalhad, Bruce Richardsond, M. Eric Gershwine, Ning Lib, , , Qianjin Lua, ,   DOI: 10.1016/j.jaut.2014.07.002
Scooped by innovIDrsrchr
Scoop.it!

Diagnosis and management of neuropsychiatric SLE : Nature Reviews Rheumatology : Nature Publishing Group

Diagnosis and management of neuropsychiatric SLE : Nature Reviews Rheumatology : Nature Publishing Group | Lupus (SLE) | Scoop.it
RT @NatRevRheumatol: NEW review - Diagnosis and management of #neuropsychiatric #SLE £ http://t.co/H2XHzMqake #lupus
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

Diagnosis and management of neuropsychiatric SLE

Diagnosis and management of neuropsychiatric SLE | Lupus (SLE) | Scoop.it
From BioPortfolio: In systemic lupus erythematosus (SLE), central nervous system involvement can present as various neurological and psychiatric features, as a primary manifestati...
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

Low Vitamin D Linked With Worse Lupus - MedPage Today

Low Vitamin D Linked With Worse Lupus - MedPage Today | Lupus (SLE) | Scoop.it
MedPage Today Low Vitamin D Linked With Worse Lupus MedPage Today Low levels of vitamin D among patients with systemic lupus erythematosus (SLE) were associated with greater disease activity and an increased likelihood of cardiovascular risk...
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

New Antibody Shows Promise in Lupus

New Antibody Shows Promise in Lupus | Lupus (SLE) | Scoop.it
Initial clinical studies of epratuzumab in patients with active, moderate-to-severe systemic lupus erythematosus are suggesting promise for this monoclonal antibody.
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

While Rheumatologists Would Welcome Novel Biologics for the Treatment of ... - PharmiWeb.com (press release)

While Rheumatologists Would Welcome Novel Biologics for the Treatment of ... - PharmiWeb.com (press release) | Lupus (SLE) | Scoop.it
While Rheumatologists Would Welcome Novel Biologics for the Treatment of Systemic Lupus Erythematosus (SLE) Reimbursement Challenges Are ExpectedA Substantial Need Remains for Emerging SLE Biologics That Can Prevent Acute Flares and That Treat Severe...
more...
No comment yet.
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Abatacept fails to treat lupus nephritis

Abatacept fails to treat lupus nephritis | Lupus (SLE) | Scoop.it
RT @philipcrobinson: Abatacept strikes out in #lupus nephritis http://t.co/s3XEjOuope from @ACRheum

 

ABSTRACT

Objective. To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis. An additional exploratory objective was to assess the potential of abatacept to induce ‘clinical tolerance’, defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy.

Methods. Patients (n=134) with active lupus nephritis were studied in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus regimen of low-dose cyclophosphamide followed by azathioprine. The primary efficacy outcome was the frequency of complete response (CR) at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group who had achieved CR status at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/d).

Results. There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. Thirty-three percent of subjects in the treatment group and 31% of subjects in the control group achieved CR status at week 24. Fifty percent of subjects in the treatment group who met CR criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their CR status through week 52.

Conclusion: The addition of abatacept to a regimen of cyclophosphamide followed by azathioprine did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered. © 2014 American College of Rheumatology.


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, August 17, 2014 11:15 AM

Abstract

 

Treatment of lupus nephritis with abatacept: The abatacept and cyclophosphamide combination efficacy and safety studyThe ACCESS Trial Group

DOI: 10.1002/art.38790

Copyright © 2014 American College of Rheumatology

Issue

Arthritis & Rheumatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Sirukumab: a novel therapy for lupus nephritis?, Expert Opinion on Investigational Drugs

Sirukumab: a novel therapy for lupus nephritis?, Expert Opinion on Investigational Drugs | Lupus (SLE) | Scoop.it

Introduction: Lupus nephritis (LN) is a significant contributor to morbidity and mortality in systemic lupus erythematosus (SLE). Current therapies for LN are limited by significant toxicities and high rates of relapse. A clear and present need exists for the development of effective, targeted and well-tolerated treatment strategies for LN.

Areas covered: In this review, the authors examine sirukumab, a monoclonal antibody with high affinity for IL-6, as a novel agent with potential for use in the treatment of SLE and LN in particular. Their review focuses on the available data on the use of sirukumab in patients. Data from Phase I trials would indicate that sirukumab is generally safe and well tolerated. This review also reports the dose-dependent decreases in absolute neutrophil count and platelet count. To date, data for sirukumab in the treatment of SLE and LN are limited, but preliminary data suggest improvement in patient-reported outcomes, and transient improvement in clinical parameters.

Expert opinion: Considering scientific literature regarding IL-6 and the IL-6 receptor antagonist tocilizumab, one could extrapolate that sirukumab has the potential to treat LN by acting acutely and locally at the site of renal injury, as well as chronically by modulating the abnormal B- and T-cell subsets observed in SLE patients. However, the clinical efficacy of sirukumab in SLE and LN, in particular, remains to be seen in Phase III trials, and efficacy data in both the induction and maintenance phases of LN treatment will be of interest.




Read More: http://informahealthcare.com/doi/abs/10.1517/13543784.2014.950837


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, September 10, 2014 12:35 PM

Drug Evaluation

Sirukumab: a novel therapy for lupus nephritis?

 

Posted online on September 5, 2014. (doi:10.1517/13543784.2014.950837)HTMLPDF (271 KB)PDF Plus (331 KB)ReprintsPermissionsUma Thanarajasingam1 & Timothy B Niewold †21Division of Rheumatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA2Division of Rheumatology and Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA +1 507 284 8450; +1 507 284 0564;niewold.timothy@mayo.edu†Author for correspondence




Read More: http://informahealthcare.com/doi/abs/10.1517/13543784.2014.950837

Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Epigenetics in the treatment of systemic lupus erythematosus: Potential clinical application

Epigenetics in the treatment of systemic lupus erythematosus: Potential clinical application | Lupus (SLE) | Scoop.it

Highlights

 

Epigenetic regulation plays a vital role in the development of SLE.

miRNAs are promising biomarkers for the diagnosis and therapeutic outcome of SLE.

HDAC1 inhibitors and anti-miRNA agents have a therapeutic potential in SLE.

 

Abstract

The current treatments of systemic lupus erythematosus (SLE) have been based on the use of immunosuppressive drugs which are linked to serious side effects. The more effective therapeutic approaches with minimal or no side effects for SLE patients are hard to develop, mainly due to the complexity of the disease. The discovery of pharmacoepigenetics provides a new way to solve this problem. Epigenetic modifications can influence drug efficacy by altering gene expression via changing chromatin structure. Although still in early development, epigenetic studies in SLE are expected to reveal novel therapeutic targets and disease biomarkers in autoimmunity. For example, miRNAs, which have been identified to govern many genes including drug targets, are altered in disease development and after drug administration. This review aims to present an overview of current epigenetic mechanisms involved in the pathogenesis of SLE, and discuss their potential roles in clinical and pharmacological applications.


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, October 22, 2014 5:42 AM
Clinical Immunology

Volume 155, Issue 1, November 2014, Pages 79–90

Review Epigenetics in the treatment of systemic lupus erythematosus: Potential clinical applicationYu Guoa, Amr H. Sawalhab, Qianjin Lua, ,   DOI: 10.1016/j.clim.2014.09.002
Scooped by innovIDrsrchr
Scoop.it!

Sle Difficult To Diagnos And Could Prove To Be Fatal - Bernama

Sle Difficult To Diagnos And Could Prove To Be Fatal - Bernama | Lupus (SLE) | Scoop.it
Sle Difficult To Diagnos And Could Prove To Be Fatal
Bernama
This disorder could prove to be fatal, yet many are oblivious of the disease called Systemic Lupus Erithematosus (SLE).
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

Treated SLE patients displayed reduced chemokine biomarkers | Rheumatology

Treated SLE patients displayed reduced chemokine biomarkers | Rheumatology | Lupus (SLE) | Scoop.it
Rheumatology | Two chemokine biomarkers displayed significantly reduced levels in patients with systemic lupus erythematosus who were treated when compared with untreated patients, according to recent study results.
more...
No comment yet.
Scooped by innovIDrsrchr
Scoop.it!

Few cutaneous lupus erythematosus patients developed SLE | Rheumatology

Few cutaneous lupus erythematosus patients developed SLE | Rheumatology | Lupus (SLE) | Scoop.it
Rheumatology | Less than 20% of patients with cutaneous lupus erythematosus later developed systemic lupus erythematosus, and most of the cases were mild, according to recent study reports.
more...
No comment yet.
Rescooped by innovIDrsrchr from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

Blisibimod, as a peptibody directed against BAFF (Anthera Pharmaceuticals) in Phase III Lupus/SLE trials

Blisibimod, as a peptibody directed against BAFF (Anthera Pharmaceuticals) in Phase III Lupus/SLE trials | Lupus (SLE) | Scoop.it

Blisibimod is a selective peptibody antagonist of the BAFF cytokine that is initially being developed as a treatment for lupus. BAFF is a tumor necrosis family member and is critical to the development, maintenance and survival of B-cells. It is primarily expressed by macrophages, monocytes and dendritic cells and interacts with three different receptors on B-cells including BAFF receptor, or BAFF-R, B-cell maturation, or BCMA, and transmembrane activator and cyclophilin ligand interactor, or TACI. The BAFF-R receptor is expressed primarily on peripheral B-cells.

 

Blisibimod, as a peptibody directed against BAFF, was developed as an alternative to antibodies and is produced in Escherichia coli. We believe Blisibimod may offer a number of potential differentiations over other BAFF antagonists such as:

Dosing flexibility with both subcutaneous and intravenous routes of deliveryThe ability to bind to both membrane-bound and soluble BAFFDistinct intellectual property as a peptibody (relative to antibody and antibody-fragments), and structurally may confer different pharmacokinetics and pharmacodynamic characteristics

 

BAFF in Autoimmune DiseasesBackground

B-cell activating factor (BAFF), otherwise known as BLyS (B lymphocyte stimulator) has been implicated in the pathogenesis of a wide range of B-cell mediated autoimmune diseases, including SLE, lupus, lupus nephritis, IgA nephropathy, rheumatoid arthritis, multiple sclerosis, Sjšgren's Syndrome, Graves' Disease. BAFF may also play a role in some hematological malignancies such as multiple myeloma. BAFF is a critical survival factor for B-cells, and is required for B-cell development and maintenance. Its involvement in B-cell survival has been demonstrated in animal studies (Kalled 2005) and in human (Avery 2003) in vitro studies. BAFF is specifically up-regulated in human and animal models of autoimmune diseases, such as SLE, Sjšgren's Syndrome, and rheumatoid arthritis (Gross 2000; Cheema 2001; Zhang 2001; Groom 2002; Kawasaki 2002). BAFF also stimulates immunoglobulin production; elevated levels have been reported in patients with IgA nephropathy. Mice that over express BAFF have demonstrated elevated levels of circulating abnormal IgA along with deposits in the kidney (McCarthy 2006 and 2011). Collectively these finding suggests that high levels of BAFF may be link to various autoimmune diseases.

BAFF in Systemic Lupus Erythematosus (SLE)

SLE (lupus) is an autoimmune disorder that involves inflammation that causes swelling, pain and tissue damage throughout the body. Lupus can affect any part of the body, but particularly the skin, heart, brain, lungs, joints and kidneys. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remission. Patients with active lupus may have a broad range of symptoms related to inflammation. Inflammation of the brain may cause seizures and other neurologic abnormalities. Inflammation of the heart may cause heart failure or sudden death. Lung inflammation causes shortness of breath. Lupus may also cause swollen joints and severe rashes. Although the cause of lupus is still not completely understood, B-cell activation and auto-antibody production are known to be central to the process. Evidence has emerged that over-expression of BAFF plays an important role in this disease process. In preclinical studies, transgenic mice created to over-express BAFF begin to exhibit symptoms similar to lupus. In addition, treatment of these same mice with BAFF antagonists appears to ameliorate the disease.

Epidemiology

Lupus primarily affects women, with a female to male ratio of about 10:1. Peak incidence occurs between ages 15 and 45, but ranges from infancy to advanced age. The Lupus Foundation estimates that approximately 1.5 million people in the United States and five million worldwide suffer from lupus.

Disease Management

Only one new therapy has been approved for lupus in the last 50 years. Other therapies such as non-steroidal anti-inflammatory drugs, or NSAIDs, corticosteroids and immunosuppressants generally act to hold back broadly the proliferation of many types of cells, including white blood cells. However, use of these agents is associated with significant adverse events and broad immune suppression.

 

BAFF in Other DiseasesIgA Nephropathy (IgAN)

IgA nephropathy (also known as BergerÕs disease) is the most common cause of primary glomerulonephritis worldwide, characterized by deposits of IgA in the kidney. These result in blood and protein leaking in to the urine. The disease typically progresses slowly but 40-50% of adults will eventually develop end-stage-renal disease and require dialysis or kidney transplant.

Epidemiology

IgAN occurs more frequently in men than women. It is also much more common in Asia than Europe or North America where it is designated as an Orphan Disease. However, in Asia, IgAN accounts for approximately 45% of cases of primary glomerulonephritis.

Disease Management

Current treatment of IgAN is non-specific and not different to the treatment of other glomerulonephropathies. These include blood pressure control and reduction of proteinuria with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers (ARBs). Corticosteroids and immunosuppressive therapy are used in some patients to treat underlying inflammation. If successful in clinical studies, blisibimod would be the first targeted specific therapy to reduce production of immunogenic IgA and thereby prevent kidney damage and disease progression.

Blisibimod Program

Blisibimod is a fusion polypeptide protein (or peptibody) consisting of a novel BAFF binding domain fused to the N-terminus of the Fc region of human antibody. Blisibimod binds to BAFF and inhibits the interaction of BAFF with its receptors.

The role of BAFF in lupus has recently been clinically validated in multiple late-stage clinical studies with an anti-BAFF antibody. We intend to advance the development of our BAFF antagonist, blisibimod, to exploit its broad potential clinical utility in autoimmune diseases, with initial focus on lupus. Blisibimod demonstrates anti-BAFF activity and has been shown to be safe and effective in selectively modulating and reducing B-cells in two Phase 1 clinical studies in lupus patients. BAFF is elevated in patients with IgAN. In ex-vivo studies of cells from patients with IgAN BAFF inhibition resulted in significant decreases in IgA production. We believe Blisibimod may offer a number of potential differentiations over other BAFF antagonists, as well as potentially other novel B-cell directed therapies including:

Dosing flexibility with both subcutaneous and intravenous routes of deliverySelective modulation and reduction of B-cellThe ability to bind to both membrane-bound and soluble BAFFDistinct intellectual property as a peptibody (relative to antibody and antibody-fragments), and structurally may confer different pharmacokinetics and pharmacodynamic characteristics

 

 


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, December 12, 2013 3:28 AM
BLyS or BAFF in Lupus and Other Autoimmune Diseases

B-cell activating factor (BAFF), otherwise known as BLyS (B lymphocyte stimulator) has been implicated in the pathogenesis of a wide range of B-cell mediated autoimmune diseases, including SLE, lupus, lupus nephritis, IgA nephropathy, rheumatoid arthritis, multiple sclerosis, Sjšgren's Syndrome, Graves' Disease. BAFF may also play a role in some hematological malignancies such as multiple myeloma. BAFF is a critical survival factor for B-cells, and is required for B-cell development and maintenance. Its involvement in B-cell survival has been demonstrated in animal studies (Kalled 2005) and in human (Avery 2003) in vitro studies. BAFF is specifically up-regulated in human and animal models of autoimmune diseases, such as SLE, Sjšgren's Syndrome, and rheumatoid arthritis (Gross 2000; Cheema 2001; Zhang 2001; Groom 2002; Kawasaki 2002). BAFF also stimulates immunoglobulin production; elevated levels have been reported in patients with IgA nephropathy. Mice that over express BAFF have demonstrated elevated levels of circulating abnormal IgA along with deposits in the kidney (McCarthy 2006 and 2011). Collectively these finding suggests that high levels of BAFF may be link to various autoimmune diseases.

 

From Anthera