title: Ephedrine treatment for autoimmune myasthenia gravis.
abstract: We studied the effect and safety of ephedrine as add-on treatment for patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG), who do not sufficiently respond to standard treatment. Four patients with AChR MG were included in a placebo-controlled, double-blind, and randomised, multiple crossover series of n-of-1 trials. Each n-of-1 trial consisted of 3 cycles, in which two 5-day intervention periods were followed by 2 days washout. In each cycle, ephedrine 50 mg daily in 2 doses was compared with placebo in the alternate treatment period. Primary outcome was a change in QMG score. Add-on treatment with ephedrine compared with placebo improved QMG score by 1.0 point (95% confidence interval 0.21-1.79), which was significant for the group of trial patients as well as for the population treatment effect. Ephedrine also showed a significant trial average treatment effect for all secondary outcomes, improving MG Composite by 2.7, MG-ADL by 1.0 and VAS score for muscle strength by 1.1. Adverse events were mild and included palpitations, tremor and restlessness. Although all ECGs were normal, ephedrine prolonged the corrected QT interval. Ephedrine as add-on treatment for myasthenia gravis resulted in a small but consistent reduction of symptoms and weakness in patients with moderate disease severity.
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.f.lipka@lumc.nl.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Lipka
authors.affiliation: Department of Clinical Genetics and EMGO Institute for Health and Care Research, section Community Genetics & Public Health Genomics, VU University Medical Center, Amsterdam, The Netherlands; Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vrinten
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kirsten J M
authors.initials: KJ
authors.lastname: Schimmel
authors.affiliation: Department of Clinical Genetics and EMGO Institute for Health and Care Research, section Community Genetics & Public Health Genomics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martina C
authors.initials: MC
authors.lastname: Cornel
authors.affiliation: Department of Care, Section Pharmaceutical Care, National Health Care Institute, Diemen, The Netherlands.
authors.forename: Marja R
authors.initials: MR
authors.lastname: Kuijpers
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Yechiel A
authors.initials: YA
authors.lastname: Hekster
authors.affiliation: Department of Clinical Genetics and EMGO Institute for Health and Care Research, section Community Genetics & Public Health Genomics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Weinreich
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan J G M
authors.initials: JJ
authors.lastname: Verschuuren
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004809:Ephedrine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology; D017063:Outcome Assessment, Health Care; D011950:Receptors, Cholinergic / Q000276:immunology*; D013566:Sympathomimetics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; D011950:Receptors, Cholinergic; D013566:Sympathomimetics; D004809:Ephedrine
keywords: Add-on therapy; Ephedrine; Myasthenia gravis; Randomised controlled trial; n-of-1 trial