ICAD: IV Immunoglobulin Therapy Shows Early Signs of Efficacy in Alzheimer's

By Peggy Peck
CHICAGO, 31 july2008 -- Mild-to-moderate Alzheimer's disease can be safely and effectively treated with intravenous immunoglobulin (IVIG) therapy, according to preliminary results from a trial reported here. Over nine months, patients randomized to IVIG demonstrated significant improvement on a number of cognitive measures compared with placebo, with no evidence of toxicity, said Norman Relkin, M.D., of Weill Cornell Medical College in New York, discussing an interim analysis of the first double-blind phase II trial of the therapy. "The key points," said Dr. Relkin at the International Conference on Alzheimer's Disease, "are that this was the first time that a controlled clinical trial of this treatment demonstrated benefit at what we believe to be an optimal dose."
He said an 18-month phase III trial was scheduled to begin this fall, recruiting at 35 clinical sites. IVIG is an appealing therapy option because "it is obtained from the plasma of healthy humans and, as such, it has the advantage of having an established safety record."
Moreover, it is literally loaded with antibodies, including antibodies against beta amyloid, he said. Asked how he could be sure that the benefit was the result of IVIG targeting beta amyloid and not attributable to other antibody activity, Dr. Relkin said that there was a dose-dependent decrease in both plasma and cerebrospinal fluid beta amyloid.
One drawback of the treatment is cost. Dr. Relkin said IVIG costs about $100 per gram and "we use 20 to 30 grams per treatment."
Another consideration is time and accessibility. Patients need to travel to a clinic where they receive infusion that typically takes at least two hours.
The trial randomized eight patients to placebo and 16 to IVIG at 0.4 g/kg every two weeks. All patients were in their early 70s and all had mild-to-moderate Alzheimer's disease. Five of the placebo patients and seven of the IVIG patients were women.
All patients were taking acetylcholinesterase inhibitors.
Efficacy endpoints were the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change.
At six months, there was no significant difference on the Alzheimer's Disease Assessment Scale (P=0.054) but at nine months, IVIG patients performed significantly better than placebo patients (P=0.009), Dr. Relkin said.
On the Clinical Global Impression of Change, the benefit was significant and apparent at six months (P=0.017), and was sustained at nine months (P=0.003), he said.
The trial was funded by the National Institutes of Health and Baxter, which is developing IVIG for Alzheimer's disease. Dr. Relkin disclosed support from Baxter Bioscience, Pfizer, Eisai, Myriad, and Smart Genetics.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Tsakanikas D, et al "Effects of uninterrupted intravenous immunoglobulin treatment of Alzheimer's disease for 9 months" ICAD 2008; Abstract 08-A-3147.