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 Jack, Mary Sano, David S Knopman, Rema Raman, Paul Szabo, David M Gelmont, Sandor Fritsch, Paul S Aisen, Alzheimer's Disease Cooperative Study, Geoffrey Ahern, Roy Yaari, Marwan Sabbagh, Nadeem Mirza, Charles Bernick, Karen Bell, R Scott Turner, Thomas Obisesan, Howard Chertkow, Yuval Zabar, David Knopman, Jacobo Mintzer, Hillel Grossman, Martin Sadowski, Chuang-Kuo Wu, Joseph Quinn, Michael Borrie, William Petrie, Brian Ott, Andrew Keegan, George Grossberg, Marwan Sabbagh, Moammed Bari, Sharon Cohen, Ralph Richter, Alan Lerner, Ruth Mulnard, Steven Potkin, Michael Rafii, John Brockington, Robin Hsiung, Susan Schultz, Jeffrey Burns, Gregory Jicha, William Burke, Steven Arnold, Anton Porsteinsson, Amanda Smith, Lon Schneider, Mary Quiceno, Edward Zamrini, Sanjay Asthana, F T Burgat, Ranjan Duara, Christopher van Dyck, Norman R Relkin, Ronald G Thomas, Robert A Rissman, James B Brewer, Michael S Rafii, Christopher H van Dyck, Clifford R Jack, Mary Sano, David S Knopman, Rema Raman, Paul Szabo, David M Gelmont, Sandor Fritsch, Paul S Aisen, Alzheimer's Disease Cooperative Study, Geoffrey Ahern, Roy Yaari, Marwan Sabbagh, Nadeem Mirza, Charles Bernick, Karen Bell, R Scott Turner, Thomas Obisesan, Howard Chertkow, Yuval Zabar, David Knopman, Jacobo Mintzer, Hillel Grossman, Martin Sadowski, Chuang-Kuo Wu, Joseph Quinn, Michael Borrie, William Petrie, Brian Ott, Andrew Keegan, George Grossberg, Marwan Sabbagh, Moammed Bari, Sharon Cohen, Ralph Richter, Alan Lerner, Ruth Mulnard, Steven Potkin, Michael Rafii, John Brockington, Robin Hsiung, Susan Schultz, Jeffrey Burns, Gregory Jicha, William Burke, Steven Arnold, Anton Porsteinsson, Amanda Smith, Lon Schneider, Mary Quiceno, Edward Zamrini, Sanjay Asthana, F T Burgat, Ranjan Duara, Christopher van Dyck
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.
© 2017 American Academy of Neurology.
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Source: PubMed