Neuromuscular disorders : NMD
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Neuromuscul. Disord. · Mar 2019
Multicenter StudySafety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study.
This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). ⋯ Baseline quadriceps muscle glycogen was low (∼6%) in most patients, generally remaining unchanged thereafter. Exploratory efficacy parameters (pulmonary function/functional capacity) generally remained stable or improved. Avalglucosidase alfa's well-tolerated safety profile and exploratory efficacy results support further avalglucosidase alfa development.
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Neuromuscul. Disord. · Apr 2017
Multicenter StudyCharacterization of pulmonary function in 10-18 year old patients with Duchenne muscular dystrophy.
Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). ⋯ Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: -8.9% [SD 2.0]; FVC%p: -8.7% [SD 1.1]; FEV1%p: -10.2% [SD 2.0]) than static airway pressures (MIP%p: -4.5 [SD 1.3]; MEP%p: -2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase.
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Neuromuscul. Disord. · Jun 2012
Multicenter StudySniff nasal inspiratory pressure and sleep disordered breathing in childhood neuromuscular disorders.
The ease of sniff nasal inspiratory pressure testing may extend application of respiratory muscle assessment to younger and cognitively-impaired children. We sought to quantify sniff nasal inspiratory pressure in childhood neuromuscular disorders, and to correlate this measure with conventional pulmonary function tests and overnight polysomnography. Thirty children (mean 9.7 ± 3.8 years, range 4.3-16.5 years) with diagnosed neuromuscular disorders (Duchenne muscular dystrophy, spinal muscular atrophy, Becker muscular dystrophy, congenital myopathy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, multi-minicore disease) underwent assessment. ⋯ A positive correlation was identified between daytime sniff nasal inspiratory pressure and maximal inspiratory pressure (r=0.58), FEV(1) (r=0.55) and FVC (r=0.46), though not with polysomnography variables (respiratory disturbance index, nadir SpO(2), peak CO(2)). Moderate prevalence of nocturnal hypoxia was observed, and 32% of children demonstrated sleep disordered breathing. Sniff nasal inspiratory pressure assessment was well tolerated, representing a promising surrogate measure for assessment of respiratory function in childhood neuromuscular disorders.
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Neuromuscul. Disord. · Jun 2010
Randomized Controlled Trial Multicenter Study Comparative StudyOral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial.
To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with 18 months follow-up. Sixty-two patients were randomised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone. Primary outcome measures included (1) seven point composite score of six clinically relevant outcomes and (2) (time-to) remission and (time-to) relapse. ⋯ Side-effects occurred significantly less frequently in the dexamethasone group. Median time to relapse was 60 (2.9) weeks in the prednisolone and 44 (4.7) weeks in the dexamethasone group (log-rank test p=0.03). In conclusion, pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies, but is a good alternative by causing substantially fewer side-effects.