Antiphospholipid Syndrome: Evaluating current treatment options
Lupus is an autoimmune disease in which people generate antibodies against their own organs. But when antibodies to phospholipid-binding proteins are involved, a variety of complications can occur.
Phospholipid-binding proteins help regulate clotting in the blood. About half of all people with lupus will make antibodies against these proteins at some point. These antiphospholipid antibodies—which can occur with or without lupus—increase the risk of miscarriages and blood clots, and can cause deep vein thrombosis and stroke.
And about 15 percent of people with lupus and antiphospholipid antibodies will have recurrent pregnancy loss or blood clots caused by antiphospholipid syndrome (APS).
Anca Askanase, M.D., M.P.H., associate professor of medicine and director of the Lupus Center at Columbia University Medical Center, and a member of the Lupus Foundation of America Medical-Scientific Advisory Council, has been treating people with autoimmune diseases for 15 years. “There have been dramatic changes in the field since I started in it,” she says. “Today, we are much more sophisticated about the management of lupus and related autoimmune blood disorders.”
One of the most surprising findings comes from one of the oldest treatments in the lupus physicians’ armamentarium: the antimalarial drug hydroxychloroquine (Plaquenil®). Approved for lupus by the Food and Drug Administration (FDA) in the 1950s, recent research suggests that Plaquenil may help lower the risk of a blood clot in people who have lupus and antiphospholipid antibodies.
Plaquenil is “such a simple drug, and yet so powerful,” says Askanase. “It is the aspirin for lupus.”
That is, Plaquenil may do for lupus what aspirin does for cardiovascular disease—reduce blood clotting and improve outcomes. And that’s especially promising, since a study by rheumatologist Doruk Erkan, M.D., at the Hospital for Special Surgery in New York City, showed that people with lupus were more likely to be resistant to aspirin’s blood-thinning effects than people without the disease.
Yet Lisa Sammaritano, M.D., also a rheumatologist at the Hospital for Special Surgery, says more research must be done to confirm that Plaquenil protects people with APS from clots.“The new data regarding Plaquenil are exciting and very promising,” says Sammaritano, “but it’s still early to know how much benefit to expect.”
Doctors are also finding that the anti-organ transplant rejection drug rituximab (Rituxan®) is helping people with the most severe variant of APS, called catastrophic APS (CAPS). This life-threatening disorder causes multiple clots in different areas of the body at one time; about half the people with CAPS will die from it. Yet since starting rituximab, Askanase’s CAPS patients have had no further blood clots. They don’t take rituximab alone, but anecdotal evidence is accumulating that rituximab makes a difference.
“I don’t use it for someone who comes in with something less severe, like deep vein thrombosis, but if it’s bad, I use Rituxan,” says Askanase. “Because the mortality with CAPS is so high, we want to use what we believe are the biggest guns.”
Better blood thinners
Blood thinners such as warfarin (Coumadin®), the traditional treatment for APS, are effective, but have drawbacks: Frequent blood tests are necessary to make sure the blood isn’t too thin or too thick. It’s off the table for pregnant women, since it’s been associated with birth defects. The level of anticoagulation can vary from too low to too high, which can lead to side effects of clotting or bleeding, respectively. And the alternative, heparin, is currently available only by injection, which is less than ideal for home use.
New oral anticoagulants may offer an alternative. Dabigatran etexilate (Pradaxa®) is a pill instead of an injection, and it keeps blood in a healthy range without the regular blood tests. But it hasn’t been studied in people with APS. Because there is no antidote to stop bleeding once it starts, more research will be necessary before doctors will consider giving it to their patients.
But that’s not the ultimate goal, says Sammaritano. Eventually, medicine needs to move in a direction that makes blood thinners unnecessary.
“Hopefully, targeted biologic therapy will eventually be available for lupus patients with APS,” says Sammaritano. “Treating the underlying immune problem that leads to the production of autoantibodies would be ideal, rather than playing catch-up by thinning the blood.”