IV Ig in Alzheimer's: Baxter's Small Phase 2 Study Warrants Phase 3 Investigation. And That Is All

First: The results are from a phase 2 study, not an all-important phase 3 study (two of which are typically required for FDA approval). As is common in a phase 2 study, different doses of the study drug were assessed.

Second: The study was small, enrolling only 21 subjects (14 with AD).

Third: The study was placebo controlled for a relatively limited time—6 months. Afterward all patients received IV Ig at various doses for 12 months.

Fourth: The difference in the ADCS-CGIC score change between treatment groups, while statistically significant, was not huge—1.36 points (-0.64 vs -2.0).

Fourth: The significant difference between the mean ADAS-cog scores at endpoint may be due to the substantial change in the mean score of control patients—15 points. It'd be nice to know when the bulk of this 15-point change in the control patients occurred: during placebo treatment or during IV Ig treatment?

Fifth: The results have not been peer reviewed.*

Perhaps the most intriguing result of Baxter's phase 2 AD study is the statistically significant associations among IV Ig treatment, brain atrophy on MR images, and clinical scores. Again, however, the study was small, and the outcome warrants confirmation in phase 3 investigations, which are ongoing or planned.

The rationale for administering IV Ig in AD is to provide nonspecific anti-amyloid antibodies. 

ADAS-cog = Alzheimer's Disease Assessment Scale, cognitive subscale; ADCS-CGIC = Alzheimer's Disease Cooperative Study, Clinical Global Impression of Change.

* While the Baxter press release indicates that these data were presented yesterday at the ongoing annual meeting of the American Academy of Neurology, I--for the life of me--cannot find the related abstract. The closest presentation from the same investigators is "Neuropsychological outcomes following 18-months of uninterrupted intravenous immunoglubulin (IVIg) treatment in patients with Alzheimer's disease (AD)." The data from this related trial are to be presented this evening.

Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.

Addendum: D'oh! Here's the AAN abstract (found in late-breaking science, which—Hmm—is to be presented as a poster this evening. It is Wednesday, isn't it?). Relkin N et al. Intravenous immunoglobulin treatment decreases rates of ventricular enlargement and cognitive decline in Alzheimer's disease. P03.294.

The 6-month data were presented at the 2008 annual meeting of the AAN. Among 23 completers, 19 had "fully evaluable data." The difference between the change in the ADCS-CGIC score of IV Ig-treated patients and that of placebo-treated patients was statistically significant (IV Ig, +0.25; placebo, -1.25; absolute difference, 1.50); however, the mean change in the ADAS-cog score was not (IV Ig, -0.38; placebo, +2.61). 

So most of the change in the ADAS-cog score of control patients at 18 months occurred while they were receiving IV Ig. It seems flukish that 6 months of upfront IV Ig therapy would provide that much neuroprotection in the treated group, whose ADAS-cog score changed by only 5 points at 18 months.