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Cited by 157Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMonoclonal and Polyclonal Antibodies Research

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A phase 3 trial of IV immunoglobulin for Alzheimer disease

Open access
Relkin, Norman R., Thomas, Ronald G., Rissman, Robert A., Brewer, James B., Rafii, Michael S., van Dyck, Christopher H., Jack, Clifford R., Sano, Mary, Knopman, David S., Raman, Rema, Szabo, Paul, Gelmont, David M., Fritsch, Sandor, Aisen, Paul S., For the Alzheimer's Disease Cooperative Study, Alzheimer's Disease Cooperative Study, Ahern, Geoffrey, Yaari, Roy, Sabbagh, Marwan, Mirza, Nadeem, Bernick, Charles, Bell, Karen, Turner, R. Scott, Obisesan, Thomas, Chertkow, Howard, Zabar, Yuval, Knopman, David, Mintzer, Jacobo, Grossman, Hillel, Sadowski, Martin, Wu, Chuang-Kuo, Quinn, Joseph, Borrie, Michael, Petrie, William, Ott, Brian, Keegan, Andrew, Grossberg, George, Sabbagh, Marwan, Bari, Moammed, Cohen, Sharon, Richter, Ralph, Lerner, Alan, Mulnard, Ruth, Potkin, Steven, Rafii, Michael, Brockington, John, Hsiung, Robin, Schultz, Susan, Burns, Jeffrey, Jicha, Gregory, Burke, William, Arnold, Steven, Porsteinsson, Anton, Smith, Amanda, Schneider, Lon, Quiceno, Mary, Zamrini, Edward, Asthana, Sanjay, Burgat, FT, Duara, Ranjan, van Dyck, Christopher·2017·Neurology
DOI 10.1212/wnl.0000000000003904PMC PMC5409846
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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 Aβ42 (but not Aβ40) levels were observed in IVIg-treated 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. CLINICALTRIALSGOV 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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Metadata

Authors
Relkin, N. R., Thomas, R. G., Rissman, R. A., Brewer, J. B., Rafii, M. S., van Dyck, C. H., Jack, C. R., Sano, M., Knopman, D. S., Raman, R., Szabo, P., Gelmont, D. M., Fritsch, S., Aisen, P. S., Study, F. T. A. D. C., Study, A. D. C., Ahern, G., Yaari, R., Sabbagh, M., Mirza, N., Bernick, C., Bell, K., Turner, R. S., Obisesan, T., Chertkow, H., Zabar, Y., Knopman, D., Mintzer, J., Grossman, H., Sadowski, M., Wu, C.-K., Quinn, J., Borrie, M., Petrie, W., Ott, B., Keegan, A., Grossberg, G., Sabbagh, M., Bari, M., Cohen, S., Richter, R., Lerner, A., Mulnard, R., Potkin, S., Rafii, M., Brockington, J., Hsiung, R., Schultz, S., Burns, J., Jicha, G., Burke, W., Arnold, S., Porsteinsson, A., Smith, A., Schneider, L., Quiceno, M., Zamrini, E., Asthana, S., Burgat, F., Duara, R., & van Dyck, C.
Affiliations
University of Southern California (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-05-02
Volume
88
Issue
18
Pages
1768-1775
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000003904
PMC
PMC5409846
OpenAlex
W2604612717
Cited by
157
References
6
Citations by year
2026: 6 · 2025: 10 · 2024: 13 · 2023: 23 · 2022: 17 · 2021: 14 · 2020: 26 · 2019: 26 · 2018: 13 · 2017: 9
FWCI
14.98
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Alzheimer's Association
  • Bristol-Myers Squibb (AG024904)
  • Eli Lilly and Company (AG024904)
  • Pfizer (AG024904)
  • AstraZeneca
  • Biogen (AG024904)
  • F. Hoffmann-La Roche (AG024904)
  • Mayo Foundation for Medical Education and Research
  • Danone
  • Baxalta
  • aTyr
  • TauRx Pharmaceuticals
  • Eisai (AG024904)
  • H. Lundbeck A/S (AG024904)
  • National Institutes of Health (BX003040, 5u01ag024904-10, U01-AG024904, AG051839, AG06786, AG005131, AG024904, AG051848, U01 AG10483, AG10483, AG000216, R01 AG37551, AG011378, UL1TR001863)
  • Genentech (AG024904)
  • National Institute on Aging (U01-AG-024904, AG050595, AG 10483, R01 AG37551, U01‐AG10483, R01AG043392, U01AG06786, RO1 AG041851, AG-06786, R43AG044860, AG000216, AG051848, AG 024904, P50AG005131, AG041851, P50AG005138, AG011378, U01AG006786, R44AG044860, U01AG010483, AG047484, AG005131, R01AG011378, R01AG034062, P30AG008051, R21AG051839, R01AG051848, T32AG000216, R01AG037551, AG051839, R01AG041851, R01AG050595, R21AG047484)
  • National Institute of Neurological Disorders and Stroke (K02NS067427)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
intravenous immunoglobulin, Alzheimer's disease, mild to moderate dementia, cognitive function, activities of daily living, amyloid-beta 42, amyloid-related imaging abnormalities, safety and tolerability
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Canada, Cognition, Double-Blind Method, Female, Humans, Male, Middle Aged, Peptide Fragments, United States, Biomarkers, Amyloid beta-Peptides, Immunoglobulins, Intravenous, Treatment Failure, Nootropic Agents, Apolipoprotein E4

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