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A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized
James F Howard1, Richard J Barohn, Gary R Cutter
1Department of Neurology, University of North Carolina, 2200 Physicians Office Building, CB 7025, 170 Manning Drive, Chapel Hill, North Carolina, 27599-7025, USA. howardj@neurology.unc.edu
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.
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