IVIG Slows Brain Atrophy in Mild to Moderate Alzheimer's

Major Finding: Treatment with a range of doses of IVIG for 18 months resulted in a mean increase of 6.7% in lateral ventricular volume, which was significantly lower than the 12.3% increase observed with placebo.

Data Source: A double-blind, placebo-controlled, randomized phase II trial of 24 patients with mild-to-moderate Alzheimer's disease.

Disclosures: Baxter Healthcare, which produces Gammagard, the IVIG product used by the investigators, sponsored the study, with additional support from the Citigroup Foundation and the National Institutes of Health. Dr. Relkin reported receiving a research grant from Baxter Healthcare.

TORONTO — Intravenous immunoglobulin therapy reduced brain atrophy in patients with mild to moderate Alzheimer's disease in a small phase II trial. The finding suggests that specific IgG antibody components found in the blood product might be treatment candidates for the disease.

“Relative to what we have available right now [to treat Alzheimer's], this is a very promising outcome, and it's associated with a reduction in the rate of brain atrophy comparable to age-matched normals,” Dr. Norman Relkin said during a poster presentation at the annual meeting of the American Academy of Neurology. Enlargement of the cerebral lateral ventricles is known to occur as a consequence of brain atrophy in AD. This increase in ventricular volume is correlated with cognitive decline and increases in Alzheimer's disease neuropathology.

Dr. Relkin, who is the director of the Memory Disorders Program at New York-Presbyterian Hospital/Weill Cornell Medical Center, and his colleagues compared intravenous immunoglobulin (IVIG) therapy against placebo in a 6-month, double-blind, randomized study of 24 patients with mild to moderate AD.

In a 12-month extension phase of the study, 16 patients who originally were randomized to IVIG continued to receive the same doses of IVIG, whereas 8 placebo-treated patients were re-randomized to one of four doses of IVIG.

IVIG exhibited a dose-dependent effect on brain atrophy in which higher doses resulted in less atrophy. Among 14 IVIG-treated patients who underwent volumetric MRI at baseline and after 18 months, the yearly increase in lateral ventricle volume measured with volumetric MRI was lowest in patients treated with 0.4 mg/kg every 2 weeks (2.4%) and highest in those treated with 0.2 mg/kg every 2 weeks (11.2%).

The doses of IVIG that were given to patients ranged from 0.2 mg/kg every 2 weeks to 0.8 mg/kg every 4 weeks.

The volume of the lateral ventricles increased by a mean of 6.7% per year during treatment with IVIG (all doses combined), which was significantly lower than the 12.3% annual rate of increase observed in six placebo-treated patients.

The reduction in brain atrophy was significantly correlated with improvement in clinical outcomes at 18 months on the Clinical Global Impression of Change and the cognitive subscale of the Alzheimer's Disease Assessment Scale. Baseline characteristics of the patients were not correlated with volumetric MRI outcomes.

“We are not encouraging people to use [IVIG] off-label for Alzheimer's disease, even though it has been safe and well tolerated in these small studies,” Dr. Relkin said in an interview. “It has never been studied in the Alzheimer's population before.”

“This is a 'kitchen sink' approach, so the next step is to find what is in [IVIG] that is causing the therapeutic effect.…We know that it has a fairly good complement of antiamyloid antibodies. Those are prime candidates, but we don't know for sure yet that those are the ones responsible for a therapeutic effect,” he said.

The ventricular enlargement rate was greater with placebo (left) than with IVIG (right).

Source Courtesy Dr. Dana Moore and Dr. Norman Relkin

Major Finding: Treatment with a range of doses of IVIG for 18 months resulted in a mean increase of 6.7% in lateral ventricular volume, which was significantly lower than the 12.3% increase observed with placebo.

Data Source: A double-blind, placebo-controlled, randomized phase II trial of 24 patients with mild-to-moderate Alzheimer's disease.

Disclosures: Baxter Healthcare, which produces Gammagard, the IVIG product used by the investigators, sponsored the study, with additional support from the Citigroup Foundation and the National Institutes of Health. Dr. Relkin reported receiving a research grant from Baxter Healthcare.

TORONTO — Intravenous immunoglobulin therapy reduced brain atrophy in patients with mild to moderate Alzheimer's disease in a small phase II trial. The finding suggests that specific IgG antibody components found in the blood product might be treatment candidates for the disease.

“Relative to what we have available right now [to treat Alzheimer's], this is a very promising outcome, and it's associated with a reduction in the rate of brain atrophy comparable to age-matched normals,” Dr. Norman Relkin said during a poster presentation at the annual meeting of the American Academy of Neurology. Enlargement of the cerebral lateral ventricles is known to occur as a consequence of brain atrophy in AD. This increase in ventricular volume is correlated with cognitive decline and increases in Alzheimer's disease neuropathology.

Dr. Relkin, who is the director of the Memory Disorders Program at New York-Presbyterian Hospital/Weill Cornell Medical Center, and his colleagues compared intravenous immunoglobulin (IVIG) therapy against placebo in a 6-month, double-blind, randomized study of 24 patients with mild to moderate AD.

In a 12-month extension phase of the study, 16 patients who originally were randomized to IVIG continued to receive the same doses of IVIG, whereas 8 placebo-treated patients were re-randomized to one of four doses of IVIG.

IVIG exhibited a dose-dependent effect on brain atrophy in which higher doses resulted in less atrophy. Among 14 IVIG-treated patients who underwent volumetric MRI at baseline and after 18 months, the yearly increase in lateral ventricle volume measured with volumetric MRI was lowest in patients treated with 0.4 mg/kg every 2 weeks (2.4%) and highest in those treated with 0.2 mg/kg every 2 weeks (11.2%).

The doses of IVIG that were given to patients ranged from 0.2 mg/kg every 2 weeks to 0.8 mg/kg every 4 weeks.

The volume of the lateral ventricles increased by a mean of 6.7% per year during treatment with IVIG (all doses combined), which was significantly lower than the 12.3% annual rate of increase observed in six placebo-treated patients.

The reduction in brain atrophy was significantly correlated with improvement in clinical outcomes at 18 months on the Clinical Global Impression of Change and the cognitive subscale of the Alzheimer's Disease Assessment Scale. Baseline characteristics of the patients were not correlated with volumetric MRI outcomes.

“We are not encouraging people to use [IVIG] off-label for Alzheimer's disease, even though it has been safe and well tolerated in these small studies,” Dr. Relkin said in an interview. “It has never been studied in the Alzheimer's population before.”

“This is a 'kitchen sink' approach, so the next step is to find what is in [IVIG] that is causing the therapeutic effect.…We know that it has a fairly good complement of antiamyloid antibodies. Those are prime candidates, but we don't know for sure yet that those are the ones responsible for a therapeutic effect,” he said.

The ventricular enlargement rate was greater with placebo (left) than with IVIG (right).

Source Courtesy Dr. Dana Moore and Dr. Norman Relkin

Major Finding: Treatment with a range of doses of IVIG for 18 months resulted in a mean increase of 6.7% in lateral ventricular volume, which was significantly lower than the 12.3% increase observed with placebo.

Data Source: A double-blind, placebo-controlled, randomized phase II trial of 24 patients with mild-to-moderate Alzheimer's disease.

Disclosures: Baxter Healthcare, which produces Gammagard, the IVIG product used by the investigators, sponsored the study, with additional support from the Citigroup Foundation and the National Institutes of Health. Dr. Relkin reported receiving a research grant from Baxter Healthcare.

TORONTO — Intravenous immunoglobulin therapy reduced brain atrophy in patients with mild to moderate Alzheimer's disease in a small phase II trial. The finding suggests that specific IgG antibody components found in the blood product might be treatment candidates for the disease.

“Relative to what we have available right now [to treat Alzheimer's], this is a very promising outcome, and it's associated with a reduction in the rate of brain atrophy comparable to age-matched normals,” Dr. Norman Relkin said during a poster presentation at the annual meeting of the American Academy of Neurology. Enlargement of the cerebral lateral ventricles is known to occur as a consequence of brain atrophy in AD. This increase in ventricular volume is correlated with cognitive decline and increases in Alzheimer's disease neuropathology.

Dr. Relkin, who is the director of the Memory Disorders Program at New York-Presbyterian Hospital/Weill Cornell Medical Center, and his colleagues compared intravenous immunoglobulin (IVIG) therapy against placebo in a 6-month, double-blind, randomized study of 24 patients with mild to moderate AD.

In a 12-month extension phase of the study, 16 patients who originally were randomized to IVIG continued to receive the same doses of IVIG, whereas 8 placebo-treated patients were re-randomized to one of four doses of IVIG.

IVIG exhibited a dose-dependent effect on brain atrophy in which higher doses resulted in less atrophy. Among 14 IVIG-treated patients who underwent volumetric MRI at baseline and after 18 months, the yearly increase in lateral ventricle volume measured with volumetric MRI was lowest in patients treated with 0.4 mg/kg every 2 weeks (2.4%) and highest in those treated with 0.2 mg/kg every 2 weeks (11.2%).

The doses of IVIG that were given to patients ranged from 0.2 mg/kg every 2 weeks to 0.8 mg/kg every 4 weeks.

The volume of the lateral ventricles increased by a mean of 6.7% per year during treatment with IVIG (all doses combined), which was significantly lower than the 12.3% annual rate of increase observed in six placebo-treated patients.

The reduction in brain atrophy was significantly correlated with improvement in clinical outcomes at 18 months on the Clinical Global Impression of Change and the cognitive subscale of the Alzheimer's Disease Assessment Scale. Baseline characteristics of the patients were not correlated with volumetric MRI outcomes.

“We are not encouraging people to use [IVIG] off-label for Alzheimer's disease, even though it has been safe and well tolerated in these small studies,” Dr. Relkin said in an interview. “It has never been studied in the Alzheimer's population before.”

“This is a 'kitchen sink' approach, so the next step is to find what is in [IVIG] that is causing the therapeutic effect.…We know that it has a fairly good complement of antiamyloid antibodies. Those are prime candidates, but we don't know for sure yet that those are the ones responsible for a therapeutic effect,” he said.

The ventricular enlargement rate was greater with placebo (left) than with IVIG (right).

Source Courtesy Dr. Dana Moore and Dr. Norman Relkin