4 results
TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease
- Stephen Salloway, Elly Lee, Michelle Papka, Andrew Pain, Ena Oru, Margaret B. Ferguson, Hong Wang, Michael Case, Ming Lu, Emily C Collins, Dawn A. Brooks, John Sims
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- Journal:
- BJPsych Open / Volume 9 / Issue S1 / July 2023
- Published online by Cambridge University Press:
- 07 July 2023, p. S67
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- Article
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Aims
To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.
MethodsParticipants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]).
ResultsBaseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.
Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008).
Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001).
62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.
ConclusionThis study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.
Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.
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- By Michael H. Allen, Leora Amira, Victoria Arango, David W. Ayer, Helene Bach, Christopher R. Bailey, Ross J. Baldessarini, Kelsey Ball, Alan L. Berman, Marian E. Betz, Emily A. Biggs, R. Warwick Blood, Kathleen T. Brady, David A. Brent, Jeffrey A. Bridge, Gregory K. Brown, Anat Brunstein Klomek, A. Jacqueline Buchanan, Michelle J. Chandley, Tim Coffey, Jessica Coker, Yeates Conwell, Scott J. Crow, Collin L. Davidson, Yogesh Dwivedi, Stacey Espaillat, Jan Fawcett, Steven J. Garlow, Robert D. Gibbons, Catherine R. Glenn, Deborah Goebert, Erica Goldstein, Tina R. Goldstein, Madelyn S. Gould, Kelly L. Green, Alison M. Greene, Philip D. Harvey, Robert M. A. Hirschfeld, Donna Holland Barnes, Andres M. Kanner, Gary J. Kennedy, Stephen H. Koslow, Benoit Labonté, Alison M. Lake, William B. Lawson, Steve Leifman, Adam Lesser, Timothy W. Lineberry, Amanda L. McMillan, Herbert Y. Meltzer, Michael Craig Miller, Michael J. Miller, James A. Naifeh, Katharine J. Nelson, Charles B. Nemeroff, Alexander Neumeister, Matthew K. Nock, Jennifer H. Olson-Madden, Gregory A. Ordway, Michael W. Otto, Ghanshyam N. Pandey, Giampaolo Perna, Jane Pirkis, Kelly Posner, Anne Rohs, Pedro Ruiz, Molly Ryan, Alan F. Schatzberg, S. Charles Schulz, M. Katherine Shear, Morton M. Silverman, April R. Smith, Marcus Sokolowski, Barbara Stanley, Zachary N. Stowe, Sarah A. Struthers, Leonardo Tondo, Gustavo Turecki, Robert J. Ursano, Kimberly Van Orden, Anne C. Ward, Danuta Wasserman, Jerzy Wasserman, Melinda K. Westlund, Tracy K. Witte, Kseniya Yershova, Alexandra Zagoloff, Sidney Zisook
- Edited by Stephen H. Koslow, University of Miami, Pedro Ruiz, University of Miami, Charles B. Nemeroff, University of Miami
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- A Concise Guide to Understanding Suicide
- Published online:
- 05 October 2014
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- 18 September 2014, pp vii-x
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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- By Graham Allan, Donna M. Allen, Irwin Altman, Arthur Aron, Donald H. Baucom, Steven R. H. Beach, Ellen Berscheid, Rosemary Blieszner, Jeffrey Boase, Tyfany M. J. Boettcher, Barbara B. Brown, Abraham P. Buunk, Lorne Campbell, Daniel J. Canary, Rodney Cate, John P. Caughlin, Mahnaz Charania, Jennie Y. Chen, F. Scott Christopher, Jennifer A. Clarke, Marilyn Coleman, W. Andrew Collins, Michael K. Coolsen, Nathan R. Cottle, Carolyn E. Cutrona, Marianne Dainton, Valerian J. Derlega, Lisa M. Diamond, Pieternel Dijkstra, Steve Duck, Pearl A. Dykstra, Norman B. Epstein, Beverley Fehr, Frank D. Fincham, Helen E. Fisher, Julie Fitness, Garth J. O. Fletcher, Myron D. Friesen, Lawrence Ganong, Kelli A. Gardner, Jenny de Jong Gierveld, Robin Goodwin, Christine R. Gray, Kathryn Greene, David W. Harris, Willard W. Hartup, John H. Harvey, Kathi L. Heffner, Ted L. Huston, William J. Ickes, Emily A. Impett, Michael P. Johnson, Deborah J. Jones, Deborah A. Kashy, Janice K. Kiecolt‐Glaser, Jeffrey L. Kirchner, Brighid M. Kleinman, Galena H. Kline, Mark L. Knapp, Ascan Koerner, Jean‐Philippe Laurenceau, Kim Leon, Timothy J. Loving, Stephanie D. Madsen, Howard J. Markman, Alicia Mathews, Mario Mikulincer, Patricia Noller, Nickola C. Overall, Letitia Anne Peplau, Daniel Perlman, Sally Planalp, Urmila Pillay, Nicole D. Pleasant, Caryl E. Rusbult, Barbara R. Sarason, Irwin G. Sarason, Phillip R. Shaver, Alan L. Sillars, Jeffry A. Simpson, Susan Sprecher, Susan Stanton, Greg Strong, Catherine A. Surra, Anita L. Vangelisti, C. Arthur VanLear, Theo van Tilburg, Barry Wellman, Amy Wenzel, Carol M. Werner, Adam R. West, Sarah W. Whitton, Heike A. Winterheld
- Edited by Anita L. Vangelisti, University of Texas, Austin, Daniel Perlman, University of British Columbia, Vancouver
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- The Cambridge Handbook of Personal Relationships
- Published online:
- 05 June 2012
- Print publication:
- 05 June 2006, pp xvii-xxii
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