Rituximab shows promise for clinical problems tied to antiphospholipid antibodies

November 20, 2012, Hospital for Special Surgery

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 (), cardiac valve disease, , kidney disease (aPL-nephropathy), and/or memory problems ().

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 . "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- 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, , , and cardiac heart valve disease do not usually respond to 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.

Explore further: Autoimmune disease linked to pregnancy loss, stroke more often than you'd expect

Related Stories

Autoimmune disease linked to pregnancy loss, stroke more often than you'd expect

November 11, 2012
For years, researchers have known that antiphospholipid antibodies (aPLs) can cause pregnancy loss and clotting, but they haven't known the true scope of the problem. Now a new study provides the first estimates of the prevalence ...

Statins have potential to treat an autoimmune clotting disorder called antiphospholipid syndrome

November 11, 2012
New research suggests that statins, traditionally used for cholesterol lowering, could be used in the management of individuals who are at risk for developing clotting because they have autoimmune antiphospholipid antibodies ...

Study sheds light on pregnancy complications and overturns common belief

July 3, 2012
A study led by Hospital for Special Surgery researchers has demonstrated that women who have a specific type of antibody that interferes with blood vessel function are at risk for adverse pregnancy outcomes and that other ...

Immune drug helps patients with serious kidney disorder

July 19, 2012
A drug commonly used to treat immune disorders such as lymphoma and arthritis also benefits patients with an immune disorder of the kidneys that can lead to kidney failure, according to a study appearing in an upcoming issue ...

Recommended for you

Osteoarthritis could be treated as two diseases, scientists reveal

January 10, 2018
Scientists at The University of Manchester have discovered that most people with osteoarthritis can be subdivided into two distinct disease groups, with implications for diagnosis and drug development.

US arthritis prevalence is much higher than current estimates

November 27, 2017
New research indicates that the prevalence of arthritis in the United States has been substantially underestimated, especially among adults

Maintaining sufficient vitamin D levels may help to prevent rheumatoid arthritis

November 20, 2017
Maintaining sufficient vitamin D levels may help to prevent the onset of inflammatory diseases like rheumatoid arthritis, research led by the University of Birmingham has discovered.

Old World monkeys could be key to a new, powerful rheumatoid arthritis therapy

November 16, 2017
In the quest for a new and more effective treatment for rheumatoid arthritis, researchers from the Keck School of Medicine of USC looked to a primate that mostly roams the land in Asia, the Middle East and Africa. It was ...

Study lists foods for fighting rheumatoid arthritis symptoms and progression

November 8, 2017
A list of food items with proven beneficial effects on the progression and symptoms of rheumatoid arthritis is provided in a new study published today in Frontiers in Nutrition. The authors suggest incorporating these foods ...

Prototype equipment can detect rheumatoid arthritis

September 28, 2017
According to a first clinical study published in the scientific journal Photoacoustics, the University of Twente and various European partners have designed a device that shows the difference between healthy fingers and arthritic ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.