Disappointing Results for IVIG in Alzheimer's Study

Abstract

BOSTON – Intravenous immunoglobulin (IVIG) is down but may not be out as a potential treatment for Alzheimer's disease. In a disappointing follow-up to last year's interim data, patients with mild to moderate disease who received IVIG experienced no significant cognitive or functional benefit relative to the placebo group, Dr. Norman Relkin reported at the Alzheimer's Association International Conference 2013. But investigators in the phase III Gammaglobulin Alzheimer's Partnership (GAP) study saw some positive, though not statistically significant, results in cognition and function in the subgroup of patients with moderate disease and in those who carried the high-risk apolipoprotein E epsilon-4 (APOE epsilon-4) allele. Those hints of benefit are enough to justify keeping IVIG on the table, said Dr. Relkin, the study's lead investigator and a neurologist at New York–Presbyterian Hospital/Weill Cornell Medical Center, New York. “I think it will be some time before we know how to move forward,” he said. “But I'm optimistic that there are some signals in these data that are worthy of further study.” GAP randomized 390 patients with mild to moderate Alzheimer's to placebo or biweekly infusions of 200 or 400 mg/kg IVIG for 18 months. Of those, 309 completed the treatment. Six-month results, reported last year, were positive. But last May, after the full 18 months of treatment, there was no significant difference in the rate of cognitive decline or change in functional ability between treatment and placebo. GAP found some statistically significant biomarker differences in patients treated with IVIG, Dr. Relkin noted. These included: ▸A dose-dependent reduction in plasma beta-amyloid 42 levels.▸Dose-dependent increases in anti-oligomer and anti-fibril antibodies in cerebrospinal fluid and plasma.▸A reduction in brain fibrillar amyloid as measured by PET scans in those who received the larger IVIG dose. There was no effect on tau in cerebrospinal fluid. It's tough to pinpoint why IVIG didn't live up to its 6-month promise, Dr. Relkin said. One reason might lie in trial design and patient selection – problems that continue to plague Alzheimer's studies. “In these large clinical trials, a certain number of patients deemed to have Alzheimer's actually don't have it,” he said. The GAP study was sponsored by Baxter. Dr. Relkin receives study support from Baxter.