3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia

Donald B. Sanders, Vern C. Juel, Yadollah Harati, A. Gordon Smith, Amanda C. Peltier, Tessa Marburger, Jau Shin Lou, Robert Pascuzzi, David P. Richman, Tai Xie, Valentin Demmel, Laura R. Jacobus, Kathy L. Aleš, David P. Jacobus

Research output: Contribution to journalArticle

  • 3 Citations

Abstract

Introduction: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for≥3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). Results: Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had>30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P<0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P<0.0001). Requirement for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM.

LanguageEnglish (US)
JournalMuscle and Nerve
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Placebos
Maintenance
3,4-diaminopyridine
Pharmaceutical Preparations
Therapeutics

Keywords

  • 3,4-diaminopyridine
  • Amifampridine
  • Clinical trial
  • Eaton-Lambert syndrome
  • Efficacy
  • ELS
  • Lambert-Eaton myasthenia
  • Lambert-Eaton myasthenic syndrome
  • Lambert-Eaton syndrome
  • LEMS
  • LES
  • Timed up-and-go

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Sanders, D. B., Juel, V. C., Harati, Y., Smith, A. G., Peltier, A. C., Marburger, T., ... Jacobus, D. P. (Accepted/In press). 3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia. Muscle and Nerve. https://doi.org/10.1002/mus.26052

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia. / Sanders, Donald B.; Juel, Vern C.; Harati, Yadollah; Smith, A. Gordon; Peltier, Amanda C.; Marburger, Tessa; Lou, Jau Shin; Pascuzzi, Robert; Richman, David P.; Xie, Tai; Demmel, Valentin; Jacobus, Laura R.; Aleš, Kathy L.; Jacobus, David P.

In: Muscle and Nerve, 01.01.2018.

Research output: Contribution to journalArticle

Sanders, DB, Juel, VC, Harati, Y, Smith, AG, Peltier, AC, Marburger, T, Lou, JS, Pascuzzi, R, Richman, DP, Xie, T, Demmel, V, Jacobus, LR, Aleš, KL & Jacobus, DP 2018, '3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia' Muscle and Nerve. https://doi.org/10.1002/mus.26052
Sanders, Donald B. ; Juel, Vern C. ; Harati, Yadollah ; Smith, A. Gordon ; Peltier, Amanda C. ; Marburger, Tessa ; Lou, Jau Shin ; Pascuzzi, Robert ; Richman, David P. ; Xie, Tai ; Demmel, Valentin ; Jacobus, Laura R. ; Aleš, Kathy L. ; Jacobus, David P. / 3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia. In: Muscle and Nerve. 2018.
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abstract = "Introduction: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for≥3 months. The primary efficacy endpoint was >30{\%} deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). Results: Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had>30{\%} deterioration in 3TUG time versus 72{\%} of the 18 who tapered to placebo (P<0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P<0.0001). Requirement for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM.",
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AU - Harati, Yadollah

AU - Smith, A. Gordon

AU - Peltier, Amanda C.

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AU - Lou, Jau Shin

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AU - Richman, David P.

AU - Xie, Tai

AU - Demmel, Valentin

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AU - Aleš, Kathy L.

AU - Jacobus, David P.

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