title: A phase 3 trial of IV immunoglobulin for Alzheimer disease.
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.
  
  
  BACKGROUND
  NCT00818662.
  
  
  METHODS
  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.
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Relkin
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: James B
authors.initials: JB
authors.lastname: Brewer
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rafii
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Paul
authors.initials: P
authors.lastname: Szabo
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: David M
authors.initials: DM
authors.lastname: Gelmont
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL.
authors.forename: Sandor
authors.initials: S
authors.lastname: Fritsch
authors.affiliation: From Weill Cornell Medicine (N.R.R., P.S.), New York, NY; University of California (R.G.T., R.A.R., J.B.B.), San Diego; University of Southern California (M.S.R., R.R., P.S.A.), Los Angeles; Yale University (C.H.v.D.), New Haven, CT; Mayo Clinic (C.R.J., D.S.K.), Rochester, MN; Mount Sinai School of Medicine (M.S.), New York, NY; and Baxalta (D.M.G., S.F.), Bannockburn, IL. paisen@usc.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D002170:Canada; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000097:blood; D017211:Treatment Failure; D014481:United States
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D016756:Immunoglobulins, Intravenous; D018697:Nootropic Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)