FDA approves first treatment for Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder

2018 ◽  
Author(s):  
Keyword(s):  
Autoimmune Disorder ◽  
Myasthenic Syndrome

scholarly journals 3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome ◽  
Randomised Controlled

Abstract Background Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

UNUSUAL DECREMENTAL RESPONSE IN LAMBERT EATON MYASTHENIC SYNDROME

2015 ◽  
Vol 86 (11) ◽  
pp. e4.50-e4
Author(s):  
Girija Sadalage ◽  
Sajjad Ali ◽  
Paul Mocroft ◽  
Adrian Williams ◽  
Saiju Jacob
Keyword(s):  
High Frequency ◽  
Autoimmune Disorder ◽  
Clinical Suspicion ◽  
High Frequency Stimulation ◽  
Repetitive Nerve Stimulation ◽  
Standing Up ◽  
Neurology Clinic ◽  
History Of ◽  
Myasthenic Syndrome ◽  
Walking Difficulty

Lambert Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction caused by antibodies against voltage gated calcium channel antibodies. The neurophysiological hallmark of LEMS is incremental response to repetitive nerve stimulation, especially at high frequency stimulation.A 54-year-old gentleman presented to the Neurology clinic with a 9-month history of progressive walking difficulty. He had difficulty standing up from a sitting down position and the symptoms were worse towards the end of the day. He had a transient history of dry mouth when the symptoms started, but denied any postural dizziness, sweating or bowel/bladder symptoms. He denied having any double vision, droopy eyelids, speech or swallowing symptoms. He had lost 1.5 stones in weight over the preceding 7–8 months. Examination showed proximal muscle weakness with reduced reflexes, which could not be potentiated. A clinical suspicion of LEMS was made, but the neurophysiological examination (repeated on three occasions) showed consistently decremental response at low and high frequency stimulations.The VGCC antibody was positive (293, normal 0–45), confirming the clinical suspicion of LEMS. The AChR and MuSK antibodies were negative.This is an unusual neurophysiological finding of a decremental response in a patient with clinical and immunological evidence of LEMS.

scholarly journals 3,4-diaminopyridine Treatment for Lambert-Eaton Myasthenic Syndrome in Adults: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safetyof 3,4-diaminopyridine (3,4-DAP) in LEMS. Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Controlled Trials Register.The primary outcome Quantitative Myasthenia Gravis (QMG) muscle score and secondary outcome compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results: Six randomised controlled trials (RCT) involving 115 patients with LEMS were included. A meta-analysis of the primary outcome showed a significant improvement of 2.33 (95% CI, -2.81 to -1.85, p<0.001) in QMG muscle score after treatment with 3,4-DAP. Moreover, a meta-analysis of the secondary outcome showed that the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment(mean difference 1.63 mV, 95% CI, 0.85 to 2.41, p<0.001). The overall assessment of all included trials showed low risk of bias and low heterogeneity. Conclusioins: The pooled results demonsrated that 3,4-DAP had a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude, which are moderate to high evidence from randomized controlled trials.

scholarly journals 3,4-diaminopyridine Treatment for Lambert-Eaton Myasthenic Syndrome in Adults: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome ◽  
Randomised Controlled

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Controlled Trials Register.The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results: Six randomised controlled trials (RCT) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.33 points (95% CI, -2.81 to -1.85, p<0.001) after treatment with 3,4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.63 mV, 95% CI, 0.85 to 2.41, p<0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions: The pooled results of randomized controlled trials demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

3,4-diaminopyridine Phosphate in the Treatment of Lambert-Eaton Myasthenic Syndrome

2012 ◽  
Vol 7 (1) ◽  
pp. 56
Author(s):  
Jörn Peter Sieb ◽  
Keyword(s):  
Neuromuscular Transmission ◽  
Autoimmune Disorder ◽  
Special Treatment ◽  
Orphan Medicinal Product ◽  
Local Hospital ◽  
Correct Dose ◽  
The Us ◽  
Myasthenic Syndrome ◽  
Drug Doses ◽  
Variable Quality

3,4-diaminopyridine (3,4-DAP, amifampridine) is the leading treatment for Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder with impaired neuromuscular transmission, for which few effective medications are currently available. 3,4-DAP has been available as a therapy for LEMS in special treatment programmes for approximately 25 years. As an unlicensed drug, doses for oral administration are required to be compounded by local, hospital or other compounding pharmacies from the base chemical. Administering the correct dose of 3,4-DAP is critical; overdosing can increase the risk of seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies, have shown a wide variation in the 3,4-DAP content of compounded preparations (22.2–125.2 %, n=9) and (53.5–128.5 %, n=21), thereby reflecting the possibility of patients receiving dosages that might be above safety limits or even markedly below efficacy limits. This inconsistency results from the variable quality and instability of the base chemical and compounding errors. A formulation of 3,4-DAP phosphate salt has now been licensed in Europe and the US with orphan medicinal product status and appears to be as efficacious as the base in relieving the symptoms of LEMS.

scholarly journals Lambert-Eaton Myasthenic Syndrome in Brazil: a single center experience

2021 ◽  
Author(s):  
Icaro França Navarro Pinto ◽  
Wladimir Bocca Vieira de Rezende Pinto ◽  
Igor Braga Farias ◽  
Bruno de Mattos Lombardi Badia ◽  
Gustavo Carvalho Costa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Muscle Weakness ◽  
Autonomic Dysfunction ◽  
Autoimmune Disorder ◽  
Small Cell ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Small Cell Lung ◽  
Myasthenic Syndrome ◽  
Brazilian Cohort

Introduction: Lambert-Eaton Myasthenic Syndrome (LEMS) is an ultrarare autoimmune disorder of neuromuscular junction characterized by proximal muscle weakness, arreflexia and autonomic dysfunction due to presynaptic dysfunction caused by autoantibodies against the P/Q-type voltagegated calcium channel with diminished release of acetylcholine. LEMS can occurs as a primary autoimmune disorder or as paraneoplastic disorder with more than half of LEMS cases associated with small cell lung cancer. Objectives: The main objective of this study is described clinical, epidemiological, serological, and neurophysiological findings of a Brazilian cohort with definitive diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). Results We identified eight patients with definitive LEMS with a 2:1 male/ female prevalence, all present with proximal muscle weakness with lower limb predominance and the most common autonomic dysfunction were xeropthalmia in 100% of patients, orthostatic hypotension presented in 6 of 9 patients and erectile dysfunction in all male patients. Conclusions: LEMS should always be suspected in patients with proximal muscle weakness associated with autonomic dysfunction and in this Brazilian cohort most cases were seronegative and do not have correlation with small-cell lung cancer in contrast with the current knowledge of disease.

Update on Amifampridine as a Drug of Choice in Lambert-Eaton Myasthenic Syndrome

US Neurology ◽  
2014 ◽  
Vol 10 (02) ◽  
pp. i ◽  
Author(s):  
Shin J Oh ◽  
Jörn Peter Sieb ◽  
◽  
Keyword(s):  
Drug Application ◽  
Clinical Trial Data ◽  
Autoimmune Disorder ◽  
Phase Iii ◽  
Drug Status ◽  
Double Blind ◽  
Drug Of Choice ◽  
Qt Intervals ◽  
The Us ◽  
Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a disabling autoimmune disorder involving impairment of neuromuscular transmission and producing serious muscle weakness, for which few effective medications are currently available. 3,4-diaminopyridine (3,4-DAP, INN/USAN: amifampridine) is the leading treatment for LEMS and has been available for over 25 years as an unapproved drug under treatment and expanded access protocols filed with the US Food and Drug Administration (FDA) or from compounding pharmacies in the US. Administering the correct dose of 3,4-DAP is critical—overdosing can increase the risk for seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies have shown a wide variation in the 3,4-DAP content of compounded preparations. A tablet formulation of 3,4-DAP phosphate salt (FIRDAPSETM) has been licenced in Europe with orphan medicinal product status since 2009 and appears to be as efficacious as the base in relieving the symptoms of LEMS. The product has also received orphan drug status in the US and is currently being evaluated in a multicenter, double-blind, placebo-controlled phase III trial to support New Drug Application (NDA) approval in the US. A recent safety trial in healthy volunteers using doses at and above normal levels has shown no effect on QT intervals, heart rate, or cardiac depolarization. Based on available clinical trial data, amifampridine phosphate was recently given Breakthrough Therapy designation by the FDA, which may enable fast-track NDA approval, thus increasing the potential for more patients with LEMS to receive an effective therapy.

Evans' syndrome- haemolytic anaemia with thrombocytopenia - a rare autoimmune disorder

2017 ◽  
Vol 6 (4) ◽  
pp. 237
Author(s):  
Majed Momin ◽  
Anamika Aluri ◽  
Santhosh Reddy ◽  
NandaKishore Pasupala
Keyword(s):  
Haemolytic Anaemia ◽  
Autoimmune Disorder ◽  
Evans Syndrome
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