A phase 3 trial of IV immunoglobulin for Alzheimer disease

Norman R. Relkin, Ronald G. Thomas, Robert A. Rissman, James B. Brewer, Michael S. Rafii, Christopher H. Van Dyck, Clifford R Jr. Jack, Mary Sano, David S Knopman, Rema Raman, Paul Szabo, David M. Gelmont, Sandor Fritsch, Paul S. Aisen

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Abstract

Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. Results: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Ab42 (but not Ab40) levels were observed in IVIgtreated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Conclusions: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. Clinicaltrials.gov identifier: NCT00818662. Classification of evidence: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

Original languageEnglish (US)
Pages (from-to)1768-1775
Number of pages8
JournalNeurology
Volume88
Issue number18
DOIs
StatePublished - May 2 2017

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Intravenous Immunoglobulins
Alzheimer Disease
Placebos
Cognition
Safety
Chills
Brain Edema
Activities of Daily Living
Exanthema
Amyloid
Respiratory Tract Infections
Albumins
Outcome Assessment (Health Care)
Equipment and Supplies
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Relkin, N. R., Thomas, R. G., Rissman, R. A., Brewer, J. B., Rafii, M. S., Van Dyck, C. H., ... Aisen, P. S. (2017). A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology, 88(18), 1768-1775. https://doi.org/10.1212/WNL.0000000000003904

A phase 3 trial of IV immunoglobulin for Alzheimer disease. / Relkin, Norman R.; Thomas, Ronald G.; Rissman, Robert A.; Brewer, James B.; Rafii, Michael S.; Van Dyck, Christopher H.; Jack, Clifford R Jr.; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M.; Fritsch, Sandor; Aisen, Paul S.

In: Neurology, Vol. 88, No. 18, 02.05.2017, p. 1768-1775.

Research output: Contribution to journalArticle

Relkin, NR, Thomas, RG, Rissman, RA, Brewer, JB, Rafii, MS, Van Dyck, CH, Jack, CRJ, Sano, M, Knopman, DS, Raman, R, Szabo, P, Gelmont, DM, Fritsch, S & Aisen, PS 2017, 'A phase 3 trial of IV immunoglobulin for Alzheimer disease', Neurology, vol. 88, no. 18, pp. 1768-1775. https://doi.org/10.1212/WNL.0000000000003904
Relkin NR, Thomas RG, Rissman RA, Brewer JB, Rafii MS, Van Dyck CH et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology. 2017 May 2;88(18):1768-1775. https://doi.org/10.1212/WNL.0000000000003904
Relkin, Norman R. ; Thomas, Ronald G. ; Rissman, Robert A. ; Brewer, James B. ; Rafii, Michael S. ; Van Dyck, Christopher H. ; Jack, Clifford R Jr. ; Sano, Mary ; Knopman, David S ; Raman, Rema ; Szabo, Paul ; Gelmont, David M. ; Fritsch, Sandor ; Aisen, Paul S. / A phase 3 trial of IV immunoglobulin for Alzheimer disease. In: Neurology. 2017 ; Vol. 88, No. 18. pp. 1768-1775.
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AU - Jack, Clifford R Jr.

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AU - Raman, Rema

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N2 - Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. Results: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Ab42 (but not Ab40) levels were observed in IVIgtreated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Conclusions: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. Clinicaltrials.gov identifier: NCT00818662. Classification of evidence: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

AB - Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. Results: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Ab42 (but not Ab40) levels were observed in IVIgtreated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Conclusions: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. Clinicaltrials.gov identifier: NCT00818662. Classification of evidence: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

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