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, Dapper Study Team, 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, Dapper Study Team

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. Muscle Nerve 57: 561-568, 2018.

Keywords: 3,4-diaminopyridine; ELS; Eaton-Lambert syndrome; LEMS; LES; Lambert-Eaton myasthenia; Lambert-Eaton myasthenic syndrome; Lambert-Eaton syndrome; amifampridine; clinical trial; efficacy; timed up-and-go.

© 2017 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Study design schematic. 3,4‐DAP, 3,4‐diaminopyridine base.
Figure 2
Figure 2
CONSORT (Consolidated Standards of Reporting Trials) diagram. 3,4‐DAP, 3,4‐diaminopyridine base.
Figure 3
Figure 3
Percentage change from baseline in 3TUG test at 2 h after dosing versus time, by treatment group. 3TUG, triple timed up‐and‐go. *P < 0.05, **P < 0.01, one‐way ANCOVA, with the baseline 3TUG as the covariate. 3,4‐DAP, 3,4‐diaminopyridine base; A, afternoon; ANCOVA, analysis of covariance; 3TUG, triple timed up ‐and ‐go; E, evening; M, morning.

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