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. Muscle Nerve 57: 561–568, 2018

3,4‐diaminopyridine in Lambert‐Eaton myasthenic syndrome: Concerns regarding presentation of previous studies

“…In both studies, DAP base and phosphate were well tolerated without any serious side effects . Thus, the definitive objective evidence of efficacy of 3,4‐DAP was shown in these 2 studies, contrary to the claims by Sanders and colleagues …”

“…The Sanders et al . study represents another contribution to the efficacy data for DAP in LEMS . Thus, there are at least 6 double‐blind studies documenting definitive objective evidence of support for 3,4‐DAP base or phosphate as symptomatic treatment of LEMS.…”

“…I have identified what I consider to be a major error in the study by Sanders and colleagues with regard to their comments about 2 previous studies . In the introductory section, they stated that “two other studies failed to provide definitive objective evidence of efficacy of 3,4‐DAP,” which is in contrast to the actual conclusions of those studies .…”

Validation of the triple timed up‐and‐go test in Lambert‐Eaton myasthenia

“…This study was a secondary analysis of data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) clinical trial, a double-blind, placebo-controlled withdrawal study of DAP in patients with LEM (NCT01511978). 22 The trial consisted of 4 stages (refer to Figure S1 in the Supplementary Material online): Acclimation (0.5 day); Baseline (2 days); Withdrawal (up to 3.5 days); and DAP Reinstitution (0.5-2 days). Data from participants who completed at least the acclimation and baseline observation stages were included in this analysis.…”

“…Because the goal of this validation study was to evaluate 3TUG performance over time in participants who are clinically stable (continuous DAP) and clinically changing (controlled DAP withdrawal), between-group comparisons of outcome measures for those who continued DAP and those who were withdrawn from DAP were not performed; these have been reported previously. 22 All analyses were performed using a percentage change from Baseline rather than the absolute values at the prespecified time-points. Data were analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina).…”