Rituximab appears to benefit clinical problems tied to antiphospholipid antibodies

FDA Highlights by Bruce Sylvester – According to a study published online on Nov. 20, 2012 in Arthritis and Rheumatism, rituximab appears to benefit patients with antiphospholipid antibodies (aPLs) who suffer from aPL-related clinical problems that are unresponsive to anticoagulation therapy, such as cardiac disease and kidney disease.

“This is the first study to systematically analyse rituximab in aPL-positive patients,” said investigator and lead author Doruk Erkan, MD, Hospital for Special Surgery, New York, New York. “Rituximab may have a role in treating a subgroup of aPL patients.”

As background the authors noted that aPLs can increase the production of proteins that cause inflammation and the clot formation. While some aPL-positive individuals are asymptomatic, others have antiphospholipid syndrome (APS) and suffer venous thrombosis, arterial thrombosis or fetal loss. Patients with sonon-criteria APS can have thrombocytopenia, cardiac valve disease, skin ulcers, kidney disease, and cognitive dysfunction.

For this phase 2 study, the investigators enrolled 19 aPL-positive patients with thrombocytopenia, cardiac valve disease, skin ulcers, aPL-nephropathy, and/or cognitive dysfunction. The subjects received 2 doses of rituximab 1,000 mg on days 1 and 15.

Investigators created aPL profiles and clinical outcome measures at baseline, at day 30, and then monthly out to 6 months.

At 24 weeks, they found that:

 

• Of the 5 patients with cognitive dysfunction, 3 had a complete response and 1 had a partial response.

• Of the 4 patients with thrombocytopenia, 1 had a complete response and another had a partial response.

• Of the 5 patients with skin ulcers, 3 had complete responses and 1 had a partial response.

• One of the 2 patients with aPL-nephropathy had a partial response.

• None of the 3 patients with cardiac valve disease had a response.

• The antiphospholipid antibody profiles of all patients did not change throughout the study.

“The low platelet counts, destruction of red blood cells causing anaemia, 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.”