VANCOUVER—Patients with mild to moderate Alzheimer’s disease who received IV immunoglobulin (IVIG) were stable and did not experience further cognitive decline after three years of follow-up, according to results from a small, phase II clinical trial presented at the 2012 Alzheimer’s Association International Conference.
Four patients who were initially randomized to IVIG at a dose of 0.4 g/kg every two weeks had no changes from their pretreatment baseline scores on measures of cognition, daily function, behavior, global outcome, and caregiver burden after 36 months.
“It is a remarkable result … an unexpected finding,” said Norman Relkin, MD, PhD, Associate Professor of Clinical Neurology and Neuroscience, Weill Cornell Medical College, in New York City.
IVIG, a mixture of human IgG antibodies that is obtained from the blood plasma of healthy young donors, has been used to treat other disorders but is not approved to treat Alzheimer’s disease. “IVIG is a candidate treatment for Alzheimer’s disease, because it contains naturally occurring antiamyloid antibodies and can alter the function of the immune system to reduce harmful effects of inflammation,” noted Dr. Relkin.
Dr. Relkin’s group sought to determine the long-term effects of IVIG in patients with mild to moderate Alzheimer’s disease. A total of 24 patients had participated in a previously reported phase II, double-blind, placebo-controlled study. Those participants had undergone six months of placebo-controlled treatment that was followed by a 12-month open-label extension during which all subjects received IVIG.
Sixteen of the originally enrolled patients subsequently consented to a continuation of treatment beginning at month 18 and received treatment through 36 months. All persons underwent clinical evaluations every six months, which included a battery of cognitive, functional, and behavioral tests.
The four patients who were initially randomized to IVIG at a dose of 0.4 g/kg every two weeks had the best outcome among all participants. Eleven patients who received IVIG at various doses for the full 36 months had favorable outcomes regarding cognition, behavior, and daily function.
In addition, five patients who were initially treated with placebo and then switched to IVIG had the least favorable outcomes but showed signs of stabilization after 18 months when they switched to the IVIG dose of 0.4 g/kg every two weeks.
“This is the first study to report long-term stabilization of Alzheimer’s disease symptoms with IVIG treatment over a period of 36 months,” Dr. Relkin commented. “Most patients with Alzheimer’s disease decline measurably in three to six months if untreated and within a year of initiating currently available treatments. Patients who received IVIG for a full 36 months in this study had less than expected decline.”
The IVIG infusions were generally well tolerated in the patients, according to Dr. Relkin, who noted that some constitutional symptoms and behavior changes occurred. However, no unexpected side effects were associated with long-term treatment. Furthermore, all patients were able to receive IVIG infusions at home throughout the extension study.
In addition to the small sample size of the study, other limitations include the high cost of IVIG and the fact that supply of the drug is limited.
The GAP (160701) phase III trial, which is in progress, is assessing the safety and efficacy of 18 months of IVIG treatment in 390 patients with mild to moderate Alzheimer’s disease. Results are expected in the first half of 2013.