Literature DB >> 23512355

A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.

James F Howard1, Richard J Barohn, Gary R Cutter, Miriam Freimer, Vern C Juel, Tahseen Mozaffar, Michelle L Mellion, Michael G Benatar, Maria Elena Farrugia, Jing Jing Wang, Suneil S Malhotra, John T Kissel.   

Abstract

INTRODUCTION: Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5).
METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG).
RESULTS: Six of 7 patients treated with eculizumab for 16 weeks (86%) achieved the primary endpoint of a 3-point reduction in the quantitative myasthenia gravis (QMG) score. Examining both treatment periods, the overall change in mean QMG total score was significantly different between eculizumab and placebo (P = 0.0144). After assessing data obtained from all visits, the overall change in mean QMG total score from baseline was found to be significantly different between eculizumab and placebo (P < 0.0001). Eculizumab was well tolerated.
CONCLUSION: The data suggest that eculizumab may have a role in treating severe, refractory MG.
Copyright © 2013 Wiley Periodicals, Inc.

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Year:  2013        PMID: 23512355     DOI: 10.1002/mus.23839

Source DB:  PubMed          Journal:  Muscle Nerve        ISSN: 0148-639X            Impact factor:   3.217


  65 in total

Review 1.  Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis.

Authors:  Jeffrey T Guptill; Madhu Soni; Matthew N Meriggioli
Journal:  Neurotherapeutics       Date:  2016-01       Impact factor: 7.620

2.  Development of Autologous C5 Vaccine Nanoparticles to Reduce Intravascular Hemolysis in Vivo.

Authors:  Lingjun Zhang; Wen Qiu; Stephen Crooke; Yan Li; Areeba Abid; Bin Xu; M G Finn; Feng Lin
Journal:  ACS Chem Biol       Date:  2017-01-12       Impact factor: 5.100

3.  Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.

Authors:  Markus J Harder; Nadine Kuhn; Hubert Schrezenmeier; Britta Höchsmann; Inge von Zabern; Christof Weinstock; Thomas Simmet; Daniel Ricklin; John D Lambris; Arne Skerra; Markus Anliker; Christoph Q Schmidt
Journal:  Blood       Date:  2016-12-27       Impact factor: 22.113

Review 4.  Therapies Directed Against B-Cells and Downstream Effectors in Generalized Autoimmune Myasthenia Gravis: Current Status.

Authors:  Grayson Beecher; Brendan Nicholas Putko; Amanda Nicole Wagner; Zaeem Azfer Siddiqi
Journal:  Drugs       Date:  2019-03       Impact factor: 9.546

Review 5.  Myasthenia gravis: an update for the clinician.

Authors:  J P Sieb
Journal:  Clin Exp Immunol       Date:  2014-03       Impact factor: 4.330

6.  Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis.

Authors:  James F Howard; Vera Bril; Ted M Burns; Renato Mantegazza; Malgorzata Bilinska; Andrzej Szczudlik; Said Beydoun; Francisco Javier Rodriguez De Rivera Garrido; Fredrik Piehl; Mariarosa Rottoli; Philip Van Damme; Tuan Vu; Amelia Evoli; Miriam Freimer; Tahseen Mozaffar; E Sally Ward; Torsten Dreier; Peter Ulrichts; Katrien Verschueren; Antonio Guglietta; Hans de Haard; Nicolas Leupin; Jan J G M Verschuuren
Journal:  Neurology       Date:  2019-05-22       Impact factor: 9.910

Review 7.  Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review.

Authors:  Jayne L Chamberlain; Saif Huda; Daniel H Whittam; Marcelo Matiello; B Paul Morgan; Anu Jacob
Journal:  J Neurol       Date:  2019-09-03       Impact factor: 4.849

8.  A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells.

Authors:  Masayuki Homma; Akiyuki Uzawa; Hitoshi Tanaka; Naoki Kawaguchi; Tetsuya Kanai; Kenji Nakajima; Masakuni Narita; Yukio Hara; Hideya Maruyama; Yasumasa Ogawa; Keiichi Himuro; Satoshi Kuwabara
Journal:  Neurotherapeutics       Date:  2017-01       Impact factor: 7.620

Review 9.  Treatment of Myasthenia Gravis in the Aged.

Authors:  Nuha M Alkhawajah; Joel Oger
Journal:  Drugs Aging       Date:  2015-09       Impact factor: 3.923

10.  Learning from the past: reflections on recently completed myasthenia gravis trials.

Authors:  Michael Benatar; James F Howard; Richard Barohn; Gil I Wolfe; Gary Cutter
Journal:  Ann N Y Acad Sci       Date:  2017-10-24       Impact factor: 5.691

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