RxPG News : Lupus

Pregnant women with lupus are at higher risk for complications

Sun, 12 Nov 2006 16:20:37 PST

( from http://www.rxpgnews.com )

Pregnant women with systemic lupus should be considered a high-risk population and should be monitored closely by both a rheumatologist and an obstetrician who specializes in caring for high-risk patients.

Women with systemic lupus who become pregnant are at significantly greater risk for death or other medical complications than are pregnant women without lupus, Duke University Medical Center researchers have found in a nationwide study of more than 18 million women.

The study, believed to be largest of its kind, suggests that pregnant women with systemic lupus should be considered a high-risk population and should be monitored closely by both a rheumatologist and an obstetrician who specializes in caring for high-risk patients, the researchers said.

"Pregnant women with lupus should never try to go through their pregnancy alone and simply hope for the best," said study leader Megan Clowse, M.D., M.P.H., assistant professor in the Division of Rheumatology. "They should stay in close contact with their doctors and report any problems immediately."

Clowse presented the findings on Sunday, Nov. 12, at the annual meeting of the American College of Rheumatology, in Washington, D.C. The study was funded by the National Institutes of Health's Building Interdisciplinary Research Careers in Women's Health program.

Lupus is an autoimmune disease in which the immune system loses its ability to distinguish between "self" and foreign substances and thus relentlessly attacks the body's own tissues and cells. Individuals with lupus often exhibit many different symptoms, including arthritis, kidney disease, rashes, fevers, anemia and sensitivity to light, among other problems.

Approximately 1.5 million Americans -- roughly 90 percent of them women -- have some type of lupus. Most patients are diagnosed during their reproductive years. Seventy percent of patients have systemic lupus, the most severe form of the disease.

All women with systemic lupus, pregnant or not, are at increased risk for death and medical complications compared to a healthy population, Clowse said. Other studies report that each year, between 0.8 percent and 3 percent of lupus patients die from the disease.

Previous research also has shown that pregnancy can increase the activity level of lupus, increasing the danger to the woman and sometimes causing problems in her fetus, according to Clowse. What was not certain, she said, is how much lupus increased a woman's health risk.

To help answer this question, Clowse's team analyzed data from more than 18 million pregnancy-related hospital admissions and discharges in the United States from 2000 to 2002. The study found that slightly more than 13,500 women with systemic lupus gave birth during this time, and 44 of the women -- 0.3 percent -- died, Clowse said.

Overall, women with systemic lupus showed a more than 20-fold greater risk of pregnancy-related death, compared with women without the disease, she said. Extrapolating this observed increase in risk to the general population suggests that for every 100,000 women with systemic lupus who would deliver a baby, approximately 325 of them would die, compared with approximately 14 deaths for every 100,000 women without the disease who would give birth, Clowse said.

"We don't want these results to scare women with lupus away from getting pregnant, especially if they have a mild form of the disease," Clowse said. "But these women really must plan their pregnancies. They may need to change their medications before they get pregnant, and they really shouldn't conceive when their lupus is active."

Clowse said patients whose lupus has been dormant for at least six months before conception are at low risk for developing active systemic lupus during pregnancy and therefore are at least somewhat less likely than women whose disease is active to experience health complications.

However, all women with systemic lupus do face elevated risks for pregnancy complications, she said. In the study population, women with systemic lupus, compared to women without the disease, were nearly six times more likely to suffer from deep vein thrombosis -- a blood clot -- and 3.5 times more likely to develop sepsis, a severe illness caused by an extreme infection of the bloodstream. Many women with lupus also were anemic or had low blood platelet counts at delivery and were three times more likely to need transfusions.

Additionally, almost 37 percent of women with lupus gave birth via cesarean section -- 15 percent higher than the national average of 22 percent. Women with lupus also were 2.5 times more likely to experience preterm labor and three times more likely to develop preeclampsia, or pregnancy-related high blood pressure, than women without lupus.

Clowse said the study's results are highly suggestive and should be taken seriously within the health care community, but she added that the study did have certain limitations.

On the plus side, the study examined a large number of patients, including patients from a variety of clinical environments, and it compared pregnancy results among women with and without lupus, she said.

However, she added, the study relied on analyzing hospital admission and discharge data, rather than on analyzing individual patient records or on examining the patients themselves.

Oral Contraceptives in Women with Lupus might be Safe

Sun, 25 Dec 2005 00:58:38 PST

( from http://www.rxpgnews.com ) In a major study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), women with either inactive or stable systemic lupus erythematosus (lupus) a disease in which the bodys immune system mistakenly attacks and damages healthy tissues of the skin, joints and internal organs were able to take oral contraceptives without increased risk of flares, or periods of increased disease activity, that characterize the disease.

Safe and effective contraception is an issue that many women of childbearing age face. But for women with lupus, doctors have often been hesitant to prescribe one of the most effective forms of contraception oral contraceptives, or the pill for fear that it might increase disease activity.

In the 15-center study of 183 women with inactive or stable lupus, those taking oral contraceptives (triphasic 35 µg.ethinylestradiol/0.5-1 mg norethindrone for twelve 28-day cycles) had no statistically significant difference in the occurrence of flares than those taking a placebo. Severe flares occurred in about 7 percent of the women, regardless of whether they received oral contraceptives or placebo. A severe flare was defined by several criteria, including the presence of new or worsening central nervous system involvement; inflammation of the blood vessels (vasculitis), kidneys (nephritis) and/or muscles (myositis); and/or blood problems, including low platelet count (thrombocytopenia) and destruction of the red blood cells (hemolytic anemia).

Mild-to-moderate flares and disease complications were similar between the two groups over the 12-month follow-up as well. Mild-to-moderate flares included fevers and inflammation of the skin, joints, the sac of fibrous tissue that surrounds the heart (pericarditis), and mucous membranes lining the nose and mouth.

Reluctance to prescribe oral contraceptives and other hormones for women with lupus arose in part from the fact that lupus is far more common in women (women with the disease outnumber men 10 to 1), and that it typically begins during the childbearing years (after the onset and before the cessation of menstruation) when female hormone levels are at their peak. In mouse models of lupus, giving estrogen makes lupus worse and, depending on the genetic background, influences the activity of white blood cells called B cells that are believed to play a key role in the disease process.

But for most women with moderate lupus that is inactive or stable, taking estrogen whether as part of an oral contraceptive or hormone replacement therapy appears to have no detrimental effect on disease activity, say co-authors Jill Buyon, M.D., of New Yorks Hospital for Joint Diseases, and Michelle Petri, M.D., M.P.H., of the Johns Hopkins University, who jointly led the study. However, they note that oral contraceptives still are not advised for women who have a history of, or are at high risk for, blood clots, because estrogens have been associated with dangerous blood clots.

The recently published study on oral contraceptives is one of two separate randomized, placebo-controlled studies that comprise the Safety of Estrogens in Lupus Erythematosus, National Assessment (SELENA) Trial. The other study, which showed no increased risk of severe flares in postmenopausal women on hormone replacement therapy, was published earlier this year (Buyon JP, et. al. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial, Ann Intern Med 2005; 142: 953-962).

There are settings in which estrogens might provide benefit, say the authors. Among women with lupus, they say, there is a high elective abortion rate approaching 23 percent of pregnancies which may reflect a failure of the birth control method used or the absence of an adequate birth control program.

Estrogen, as used in this study, appears to be safe in the majority of women with stable disease, says NIAMS Director Stephen I. Katz, M.D., Ph.D. This research brings us another step forward in improving quality of life for people with rheumatic disease.

Pro-inflammatory HDL (piHDL) is a potential biomarker for lupus atherosclerosis

Wed, 16 Nov 2005 19:26:38 PST

( from http://www.rxpgnews.com ) Groundbreaking research reported at the annual meeting of the American College of Rheumatology indicates that a certain form of the normally "good" high density lipoprotein (HDL) cholesterol linked to cardiovascular health plays a counterproductive role in people with systemic lupus erythematosus (SLE) and rheumatoid arthritis, promoting atherosclerosis (hardening of the arteries) and heart disease in many of these individuals.

The menacing HDL form is pro-inflammatory HDL (piHDL), according to research by Bevra H. Hahn, MD, Maureen McMahon, MD, and colleagues at the David Geffen School of Medicine at UCLA, and it can easily be measured and, most importantly, treated. Dr. Hahn is chief of the division of rheumatology, and Dr. McMahon is an assistant clinical professor of rheumatology.

"Traditional risk factors for atherosclerosis--including high blood pressure, increased cholesterol levels, diabetes mellitus, older age and postmenopausal status--have proved ineffective for predicting atherosclerosis in SLE patients," said Dr. Hahn, whose research is funded by the Lupus Research Institute (LRI). "Uncovering a potentially important role for pro-inflammatory HDL in the development of atherosclerotic disease in patients with SLE is an important first step toward developing strategies to prevent cardiovascular morbidity and mortality in these patients."

Dr. Hahn notes that "pro-inflammatory HDL, which is easily measured, may provide just the sign, known as a biomarker, to determine which patients are at increased risk. If this research is successful, in two years or sooner a test may be available to screen for piHD.

According to Dr. Hahn, women with lupus are about 7 to 10 times more likely than women without the disease to suffer a heart attack or stroke--just a few of the myriad serious health problems confronting the estimated 1.5 million Americans with this chronic autoimmune disease. In lupus, the body attacks its own healthy tissues and organs in a repetitive cycle of flare-ups and remissions.

In the study, Dr. Hahn measured the presence of pro-inflammatory and HDL in samples of blood plasma from 154 women with SLE, 73 age matched controls, and 50 women with rheumatoid arthritis. Compared to the control group, the HDL from those with SLE contained significantly more piHDL. "We found that almost 50 percent of SLE patients, versus approximately 4 percent of controls and 20 percent of rheumatoid arthritis patients, had piHDL," said Dr. Hahn.

In addition, piHDL was found in 8 of the 10 individuals with SLE determined to have actual atherosclerosis. The biomarker was similarly high in half of the 12 subjects with SLE that had suffered a stroke (cerebrovascular event).

"We can clearly see from these results that HDL function fails to protect against cardiovascular disease in many SLE and rheumatoid arthritis patients," Dr. Hahn concluded. "This discovery may lead to an effective test [a fluorescence assay] to identify those at increased risk for blockage of the coronary arteries so that we can start them on preventive treatments like cholesterol-lowering statins."

Epratuzumab may Serve as a Potential Treatment Option for SLE

Mon, 06 Jun 2005 10:09:38 PST

( from http://www.rxpgnews.com ) Immunomedics Inc announced patient dosing has begun for the pivotal Phase III clinical trials to further evaluate the safety and efficacy of the Company's lead drug candidate, epratuzumab, for the treatment of patients with systemic lupus erythematosus (SLE), known as lupus.

Epratuzumab has been designated by the U.S. Food and Drug Administration ( FDA ) as a Fast Track product for the potential treatment of patients with moderate and severe SLE. Epratuzumab is a humanized monoclonal antibody that targets an antigen, known as CD22, found on the surface of a certain class of lymphocytes, a type of white blood cell.

Epratuzumab has shown activity in patients with SLE with mild depletion of circulating B-lymphocytes. This suggests epratuzumab may work by modulating B-cell function, as contrasted with other B-cell antibodies that appear to require depletion of B-cells. It also implies a possible reduction in the risk of infection, which is commonly associated with lupus, and can be life-threatening. We are pleased to advance our lead drug candidate, epratuzumab, into pivotal Phase III lupus trials, and to be at the forefront of lupus therapy research, commented Ivan D. Horak, M.D., Executive Vice President, Research and Development, and Chief Scientific Officer of Immunomedics.

There is a need for a new drug that addresses and improves the quality of life for the estimated 3 to 5 million patients worldwide afflicted with lupus, a debilitating and often life-threatening disease. We are pleased that Pharmaceutical Product Development, Inc. ( Nasdaq: PPDI ) will work with us to execute these pivotal trials, said Cynthia L. Sullivan, President and Chief Executive Officer of the Company. We continue to hold discussions with potential partners for epratuzumab in all indications, with the aim of securing the best possible agreement for further development of our product and to maximize value for our shareholders.

The pivotal trials are randomized, double-blinded, placebo-controlled, multi-center studies using the BILAG ( British Isles Lupus Assessment Group ) index to monitor and assess disease activity. A high BILAG score indicates increased disease activity. The trials have been named ALLEVIATE or Alleviate Lupus Affliction with Epratuzumab and Validate its Autoimmune Safety and Efficacy. One trial, ALLEVIATE A, is for patients with severe SLE flares, and the second trial, ALLEVIATE B, is for patients with moderately active SLE.

About Epratuzumab

Epratuzumab is Immunomedics' lead product candidate being evaluated in two pivotal Phase III trials for the treatment of moderate and severe SLE. The FDA granted a Fast Track designation to the clinical development program for epratuzumab for the treatment of patients with SLE. Epratuzumab has also demonstrated good safety, tolerability, and clinical efficacy in more than 340 patients with non-Hodgkin's lymphoma, resulting in reports published in The Journal of Clinical Oncology and Clinical Cancer Research.

About Systemic Lupus Erythematosus

Systemic lupus erythematosus ( SLE ) is a serious autoimmune disease affecting approximately 1.5 million Americans, according to the Lupus Foundation of America. In the U.S., women with SLE outnumber men by a ratio of nine to one, and 80% of female patients develop lupus between the ages of 15 and 45. At present, there is no cure for lupus and no new lupus drug has been approved in the U.S. for nearly 40 years. Lupus most often results in chronic inflammation and pain affecting various parts of the body, especially the skin, joints, blood, and kidneys. The disease can be serious and life threatening. Current treatments used in medical practice include corticosteroids, nonsteroidal anti-inflammatory drugs, immunosuppressives, and antimalarials.

The FDA has recently issued a draft guideline to industry on developing drugs for the treatment of SLE that is available at fda.gov/cder/guidance/6496dft.pdf.

How lupus T cells lose IL-2

Sun, 03 Apr 2005 13:10:38 PST

( from http://www.rxpgnews.com ) Lupus is a chronic, autoimmune disease that causes inflammation, particularly of the skin, joints, blood, and kidneys. Patients with lupus produce antibodies against their own proteins. Patients also have immune T cells that produce a protein called IL-2, which normally usually protects against infection, at lower than typical levels. In a study appearing in the April 1 print edition of The Journal of Clinical Investigation, George Tsokos and colleagues from the Walter Reed Army Institute of Research explore the mechanisms underlying this decreased IL-2 production.

The researchers find that sera from lupus patients contains antibodies that bind to T cells and activate a complex cellular signaling cascade that ultimately results in decreased IL-2 production. This deficiency in IL-2 could result in the autoantibody production that occurs in lupus.

In an accompanying commentary, Gary Kammer of Arthritis Associates, Inc points out "the contribution by Tsokos and his colleaguesprovides a new appreciation and insight into how the microenvironment in lupus can further impinge on a defective T cell to inhibit IL-2 production. From such studies will come the inspiration and novel approaches necessary to develop therapeutic tools to abate disease and improve the quality of life of our patients."