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 thirty years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in LEM patients 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: 32 participants were randomized to continuous 3,4-DAP or placebo. None of the 14 receiving continuous 3,4-DAP had >30% deterioration in 3TUG time vs 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). Need 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.