Amifampridine phosphate in congenital myasthenic syndrome

Verma, Sumit; Mazell, Shawnay; Shah, Durga

doi:10.1002/mus.25230

Cited by 11 publications

(6 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mean jitter values along with clinical assessment (MGFA scores) were useful in directing treatment. We have previously shown the utility of Stim‐JA as an electrophysiological measure of improvement in 2 congenital myasthenic syndrome patients pretreatment and posttreatment with amifampridine phosphate . Similarly to the studies in adult MG patients, we propose serial jitter values as an electrophysiological biomarker in patients with JMG …”

Section: Discussionmentioning

confidence: 77%

“…We have previously shown the utility of Stim-JA as an electrophysiological measure of improvement in 2 congenital myasthenic syndrome patients pretreatment and posttreatment with amifampridine phosphate. 14 Similarly to the studies in adult MG patients, we propose serial jitter values as an electrophysiological biomarker in patients with JMG. 1,15 Grip strength and FVC percentage predicted values did not correlate with MGFA class.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Serial Stimulated Jitter Analysis In Juvenile Myasthenia Gravis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 95%

Serial Stimulated Jitter Analysis In Juvenile Myasthenia Gravis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…4,9 Therefore, a drug which improves neuromuscular transmission in MuSK-MG fulfills a true medical need. In this regard, a strong body of preclinical 2–5,9–11,15 and clinical 2,6–8,12–14,16–18,24 evidences suggests AP as a good option for the treatment of MuSK-MG patients.…”

Section: Discussionmentioning

confidence: 99%

“…A considerable amount of clinical experience with the phosphate salt of 3,4-DAP (amifampridine phosphate (AP), Firdapse ® ) has been gained, providing evidence for its efficacy and safety in different autoimmune and genetic NMJ diseases, including Lambert-Eaton myasthenic syndrome (LEMS) and congenital myasthenic syndrome (CMS). 12,13 Generally, AP has been recommended as first-line symptomatic treatment for LEMS by the European Federation of Neurological Societies (EFNS). 14 Based on MuSK-MG-specific pathogenic features, 2 recent nonclinical studies examined the effects of 3,4 DAP in MuSK mouse models, demonstrating that 3,4 DAP significantly improved neuromuscular transmission.…”

Section: Introductionmentioning

confidence: 99%

Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study

et al. 2018

View full text Add to dashboard Cite

Objective:The aim of this study is to determine the safety and the efficacy of amifampridine phosphate in muscle-specific kinase antibody-positive myasthenia gravis, in a 1:1 randomized, double-blind, placebo-controlled, switchback, double crossover study.Methods:Eligible patients had muscle-specific kinase myasthenia gravis, >18 years of age, and Myasthenia Gravis Foundation of America class II–IV with a score of ⩾9 on Myasthenia Gravis Composite scale. After the run-in phase, during which amifampridine phosphate was titrated to a tolerable and effective dosage, patients were randomized to receive placebo–amifampridine–placebo sequence or amifampridine–placebo–amifampridine sequence daily for 7 days. Then, patients switched treatment arms twice, for a total of 21 days of double-blind treatment. Safety was determined by serial assessments of adverse events/serious adverse events, physical examinations, and clinical and laboratory tests. The co-primary outcome measures included changes from baseline of Quantitative Myasthenia Gravis score and Myasthenia Gravis–specific Activities of Daily Living Profile score. The secondary outcome measures comprised changes from baseline of Myasthenia Gravis Composite score, Myasthenia Gravis Quality of Life scale—15 questions, Fatigue Severity Scale, and Carlo Besta Neurological Institute–Myasthenia Gravis scale. Statistical analyses were assessed using a switchback model for three-period, two-treatment crossover design.Results:A total of 10 patients were screened, enrolled, and treated. Transient paresthesias (60%) were the only amifampridine phosphate–related adverse events reported. Four patients were randomized to receive placebo–amifampridine–placebo sequence and three patients to receive amifampridine–placebo–amifampridine sequence. The co-primary objectives were statistically met (Quantitative Myasthenia Gravis score: p = 0.0003 and Myasthenia Gravis–specific Activities of Daily Living Profile score: p = 0.0006), as well as all the secondary endpoints (Myasthenia Gravis Composite score: p < 0.0001, Myasthenia Gravis Quality of Life scale—15 questions: p = 0.0025, Fatigue Severity Scale: p = 0.0061, and Carlo Besta Neurological Institute–Myasthenia Gravis scale: p = 0.0014).Conclusion:Despite the low number of patients, MuSK-001 study provided evidence that amifampridine phosphate, in the range of 30–60 mg daily dose, was safe and effective in treating muscle-specific kinase myasthenia gravis, suggesting the need for a large multi-center trial to confirm these results.

show abstract

“…Amifampridine (3,4-diaminopyridine phosphate) is a voltage-dependent K + channel blocker that prolongs depolarization of the presynaptic neuromuscular junction terminal and increases acetylcholine release, empowering neuromuscular transmission and muscle function [ 18 , 19 ]. Amifampridine is recommended for the symptomatic treatment of Lambert–Eaton myasthenic syndrome by the European Federation of Neurological Societies and the Food and Drug Administration in the USAs, and its efficacy has been proven in different autoimmune and genetic NMJ diseases, including anti-MuSK myasthenia gravis (MG) and congenital myasthenic syndrome (CMS) [ 20 – 23 ]. Amifampridine is rapidly absorbed after oral administration and rapidly eliminated, with the phosphate form having a short half-life of about 1.8 h [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%