Rituximab shows promise for clinical problems tied to antiphospholipid antibodies

May provide treatment option for those with harder-to-treat memory problems, skin ulcers and kidney disease

2012-11-20

(Press-News.org) Rituximab, a drug used to treat cancer and arthritis, may help patients with antiphospholipid antibodies (aPLs) who suffer from aPL-related clinical problems that do not respond to anticoagulation, such as cardiac disease and kidney disease, according to a new study by rheumatology researchers at Hospital for Special Surgery. The study appears online ahead of print, in the journal Arthritis and Rheumatism.

"This is the first study to systematically analyze rituximab in aPL-positive patients. Rituximab may have a role in treating a subgroup of aPL patients," said Doruk Erkan, M.D., senior author of the study, and an associate attending rheumatologist at Hospital for Special Surgery in New York City.

For years, researchers have known that aPLs can increase the production of certain proteins that can cause inflammation and the formation of clots. While some aPL-positive individuals are perfectly healthy, others are classified as having antiphospholipid syndrome (APS) and have venous thrombosis, arterial thrombosis or fetal loss. Patients with so-called "non-criteria APS manifestations" can have low platelet counts (thrombocytopenia), cardiac valve disease, skin ulcers, kidney disease (aPL-nephropathy), and/or memory problems (cognitive dysfunction).

Previously, researchers have shown that B-cells, a type of white blood cell, secrete aPLs and that eliminating B-cells can prevent the development of APS in mice. A number of case reports have suggested that some patients with APS may respond to rituximab. This drug, which can destroy B-cells, is currently used in patients with leukemia and rheumatoid arthritis. "The idea is if you kill the inflammatory B-cells, they can not secrete antiphospholipid antibodies that cause problems," Dr. Erkan explained.

In the current Phase II pilot trial, researchers recruited 19 aPL-positive patients with thrombocytopenia, cardiac valve disease, skin ulcers, aPL-nephropathy, and/or cognitive dysfunction. Patients were given two doses of 1,000 mg rituximab on days one and 15. Investigators measured aPL profiles and clinical outcome measures at baseline, at day 30, and then monthly up to six months.

At 24 weeks, several patients had improved outcomes. Of the five patients with cognitive dysfunction, three had a complete response and one had a partial response. Of the four patients with thrombocytopenia, one had a complete response and another had a partial response. Of the five patients with skin ulcers, three had complete responses and one had a partial response. One of the two patients with aPL-nephropathy had a partial response. None of the three patients with cardiac valve disease had a response. The antiphospholipid antibody profiles of all the patients, however, did not change throughout the study.

"Why is there a response in some patients without decreasing aPL titers?" said Dr. Erkan. "The answer for that is B-cells are very complex; they not only secrete aPL, but they also participate in the immune response by helping other inflammatory cells." In other words, they may be shutting the aPL effect down through other channels.

The authors say that rituximab may offer a potential treatment option for some non-criteria APS manifestations. This is good news, because while anticoagulation therapies can treat some of the complications seen in APS patients, they are not helpful in treating the non-criteria APS manifestations. "The low platelet counts, destruction of red blood cells causing anemia, kidney disease, memory problems, and cardiac heart valve disease do not usually respond to anticoagulation therapy," said Dr. Erkan.

"Our future goal is confirming our results with a randomized controlled trial, and we also need to try to identify which patients will respond to rituximab. We need to find the predictors of response," said Dr. Erkan.

### Other authors of the study include Michael Lockshin, M.D., Joann Vega and Glendalee Ramon, all from Hospital for Special Surgery, and Elizabeth Kozora, Ph.D., who is an adjunct scientist at HSS and both professor, Department of Medicine, National Jewish Health, and professor, Department of Psychiatry and Neurology, University of Colorado Denver Medical School.

About Hospital for Special Surgery Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopedics, No. 3 in rheumatology, No. 10 in neurology and No. 5 in geriatrics by U.S. News & World Report (2012-13), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center three consecutive times. HSS has one of the lowest infection rates in the country. From 2007 to 2011, HSS has been a recipient of the HealthGrades Joint Replacement Excellence Award. HSS is a member of the New York-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at www.hss.edu.

For more information contact: Phyllis Fisher
212-606-1197
FisherP@hss.edu

ELSE PRESS RELEASES FROM THIS DATE:

VTT: A low-carbon Finland is a great challenge, but an achievable one

2012-11-20

VTT specialists have assessed Finland's chances of achieving the 80% greenhouse gas emission reduction targets. The EU's goal for 2050 is to reduce emissions by at least 80% from the level of 1990. The goal is a tough one for Finland, but possible to achieve as long as all sectors that produce or consume energy take part. On top of this, all greenhouse gas emissions must be reduced. Finland requires new technological solutions for industrial activity, for the transport of people, goods and services, and for housing and working methods. If clean forms of energy and the ...

Europe must not lose momentum in marine biodiversity research

2012-11-20

A new Marine Board Future Science Brief presents a roadmap for marine biodiversity science in Europe and warns against complacency. The ocean provides 95% of the habitable space on Earth and harbours a vast diversity of life. Biodiversity underpins the health of the oceans and their productive ecosystems which are essential for human well-being and prosperity. But marine life is under significant threat from climate change and from increasing human impacts including pollution, overfishing and ocean acidification. Marine biodiversity research and its role in supporting ...

Gastric bypass surgery: Follow up as directed to lose more

2012-11-20

Gastric bypass patients who attended five follow-up office visits in two years as recommended by their surgeons lost nearly twice as much weight (113 lbs. vs. 57 lbs.) as patients who attended only two follow-up visits, according to a University of Pennsylvania School of Nursing study in Obesity Surgery. The global epidemic of overweight and obese people is estimated to include 1.7 billion individuals, with two-thirds of those living in the U.S. Measurement of body mass index (BMI), a calculation of height and weight, classifies obesity. Patients with severe obesity ...

Sweat glands play major role in healing human wounds, U-M research shows

2012-11-20

ANN ARBOR, Mich. — Turns out the same glands that make you sweat are responsible for another job vital to your health: they help heal wounds. Human skin is rich with millions of eccrine sweat glands that help your body cool down after a trip to the gym or on a warm day. These same glands, new University of Michigan Health System research shows, also happen to play a key role in providing cells for recovering skin wounds – such as scrapes, burns and ulcers. The findings were released online ahead of print in the American Journal of Pathology. "Skin ulcers – including ...

King's Water Research Group co-convenes global conference on food and water security

2012-11-20

A team of experts from King's College London have played a major role in delivering an international conference on food and water security in Qatar this week. The Food Security in Dry Lands (FSDL) conference has been organised in the run up to the forthcoming UN climate meeting (COP18) later this month, where 'climate-smart' agriculture is expected to be a key focus. The King's Water Research Group have contributed to the new Doha Declaration, which states that by 2022, participating countries -Qatar, Kenya, Tanzania, Chad, Egypt, Jordan, Saudi Arabia, South Africa, Nigeria, ...

Discovery of molecular pathway of Alzheimer's disease reveals new drug targets

2012-11-20

The discovery of the molecular pathway that drives the changes seen in the brains of Alzheimer's patients is reported today, revealing new targets for drug discovery that could be exploited to combat the disease. The study gives the most detailed understanding yet of the complex processes leading to Alzheimer's. Alzheimer's disease is associated with plaques made up of deposits of a molecule called amyloid between brain cells, which leads to the formation of tangles of twisted fibres made from a molecule called tau, found inside the brain cells. This causes the death ...

Frequency of alcohol consumption and cardiovascular risk factors

2012-11-20

Critique 096: Frequency of alcohol consumption and cardiovascular risk factors: implications for drinking guidelines 20 November 2012 Read the full critique here: http://www.bu.edu/alcohol-forum/critique-096-frequency-of-alcohol-consumption-and-cardiovascular-risk-factors-implications-for-drinking-guidelines-20-november-2012/ The purpose of this paper was to examine whether drinkers who consume lower-risk amounts on more frequent occasions have favourable risk factor profiles compared with those who drink more per occasion but less frequently. The authors also discuss ...

Dance boosts young girls' mental health

2012-11-20

Young girls can dance their way to better mental health. Symptoms like depression, stress, fatigue, and headaches are alleviated with regular dancing. This is shown in a study run by Anna Duberg, a physical therapist at Örebro University Hospital and a doctoral candidate at Örebro University in Sweden. Regular dance training can thereby be regarded as a strategy for preventing and treating low spirits and depression. Dance also brings enhanced self-esteem and a greater capacity to deal with everyday problems. The dance study included 112 Swedish girls 13 to 19 years ...

Scientists at Mainz University identify inhibitor of myelin formation in the central nervous system

2012-11-20

Scientists at the Mainz University Medical Center have discovered another molecule that plays an important role in regulating myelin formation in the central nervous system. Myelin promotes the conduction of nerve cell impulses by forming a sheath around their projections, the so-called axons, at specific locations – acting like the plastic insulation around a power cord. The research team, led by Dr. Robin White of the Institute of Physiology and Pathophysiology at the University Medical Center of Johannes Gutenberg University Mainz, recently published their findings in ...

Researchers build synthetic membrane channels out of DNA

2012-11-20

As reported in the journal Science, physicists at the Technische Universitaet Muenchen (TUM) and the University of Michigan have shown that synthetic membrane channels can be constructed through "DNA nanotechnology." This technique employs DNA molecules as programmable building materials for custom-designed, self-assembling, nanometer-scale structures. The researchers present evidence that their nature-inspired nanostructures may also behave like biological ion channels. Their results could mark a step toward applications of synthetic membrane channels as molecular sensors, ...

Rituximab shows promise for clinical problems tied to antiphospholipid antibodies

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: