Profile of aminopyridines for Lambert–Eaton myasthenic syndrome

Abstract:

3,4-diaminopyridine (3,4-DAP) is an effective, symptomatic treatment for Lambert–Eaton myasthenic syndrome (LEMS). Several trials have studied the effects of 3,4-DAP in small numbers of LEMS patients. We systematically reviewed all randomized trials of 3,4-DAP in LEMS to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points. Data from four randomized, placebo-controlled trials revealed that muscle-strength scores increased significantly with 3,4-DAP. Limited meta-analysis performed on two trials using the quantitative myasthenia gravis score indicated that the clinical benefits seen were modest, with an improvement in quantitative myasthenia gravis score of 2.44 points (95% confidence interval: 1.2–3.6). Meta-analysis of the mean change in compound muscle action potential amplitude following 3,4-DAP treatment revealed a significant improvement compared to placebo (1.36 mV, 95% confidence interval: 0.99–1.72). 3,4-DAP is an effective, safe, first-line symptomatic treatment for LEMS, with significant clinical and electrophysiological benefits demonstrated by meta-analysis.

Keywords::

• Lambert–Eaton myasthenic syndrome
• 3,4-diaminopyridine
• meta-analysis

Acknowledgments

We are grateful for the statistical input kindly provided by Dr AV Swan. Statistical calculations of the effects of 3,4-DAP in LEMS, and associated graphs of the meta-analyses, have previously been reported in a review of all randomized controlled trials of treatments for LEMS.⁴³ This paper is in part based on a Cochrane Review published in The Cochrane Library 2010, Issue 2 (see http://www.thecochranelibrary.com for information).⁴³ Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.

Disclosure

Dr Paul Maddison received a single honorarium for consultancy work from BioMarin. The authors report no other conflicts of interest in this work.