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 M. 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 M.; 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, RM, 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 M. ; 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.
@article{2b612c9f45754a9abc9eb5a1b43f173a,
title = "3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia",
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.",
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",
author = "Sanders, {Donald B.} and Juel, {Vern C.} and Yadollah Harati and Smith, {A. Gordon} and Peltier, {Amanda C.} and Tessa Marburger and Lou, {Jau Shin} and Pascuzzi, {Robert M.} and Richman, {David P} and Tai Xie and Valentin Demmel and Jacobus, {Laura R.} and Aleš, {Kathy L.} and Jacobus, {David P.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/mus.26052",
language = "English (US)",
journal = "Muscle and Nerve",
issn = "0148-639X",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - 3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia

AU - Sanders, Donald B.

AU - Juel, Vern C.

AU - Harati, Yadollah

AU - Smith, A. Gordon

AU - Peltier, Amanda C.

AU - Marburger, Tessa

AU - Lou, Jau Shin

AU - Pascuzzi, Robert M.

AU - Richman, David P

AU - Xie, Tai

AU - Demmel, Valentin

AU - Jacobus, Laura R.

AU - Aleš, Kathy L.

AU - Jacobus, David P.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - 3,4-diaminopyridine

KW - Amifampridine

KW - Clinical trial

KW - Eaton-Lambert syndrome

KW - Efficacy

KW - ELS

KW - Lambert-Eaton myasthenia

KW - Lambert-Eaton myasthenic syndrome

KW - Lambert-Eaton syndrome

KW - LEMS

KW - LES

KW - Timed up-and-go

UR - http://www.scopus.com/inward/record.url?scp=85041347596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041347596&partnerID=8YFLogxK

U2 - 10.1002/mus.26052

DO - 10.1002/mus.26052

M3 - Article

JO - Muscle and Nerve

T2 - Muscle and Nerve

JF - Muscle and Nerve

SN - 0148-639X

ER -