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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

New York—November 19, 2012

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 in November, 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 HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.

 

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