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

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.

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Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

Neurology ◽

10.1212/wnl.0000000000007600 ◽

2019 ◽

Vol 92 (23) ◽

pp. e2661-e2673 ◽

Cited By ~ 39

Author(s):

James F. Howard ◽

Vera Bril ◽

Ted M. Burns ◽

Renato Mantegazza ◽

Malgorzata Bilinska ◽

...

Keyword(s):

Adverse Events ◽

Myasthenia Gravis ◽

Vital Signs ◽

Standard Of Care ◽

Placebo Treatment ◽

Phase 2 ◽

Double Blind ◽

Severity Scores ◽

Quality Of Life Scale ◽

Life Scale

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

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BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/245742 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Franciska Gyulai ◽

Katalin Rába ◽

Ildikó Baranyai ◽

Enikő Berkes ◽

Tamás Bender

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Chronic Low Back Pain ◽

Low Back ◽

Double Blind ◽

Quality Of Life Scale ◽

Knee Arthrosis ◽

Scale Scores ◽

Life Scale

Background.This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design.Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo.Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale.Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee.

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Translation and validation of the 15-item Myasthenia Gravis Quality of life scale in Dutch

Muscle & Nerve ◽

10.1002/mus.25641 ◽

2017 ◽

Vol 57 (2) ◽

pp. 206-211 ◽

Cited By ~ 2

Author(s):

Ellen Strijbos ◽

Fania R. Gärtner ◽

Jan J. Verschuuren

Keyword(s):

Quality Of Life ◽

Myasthenia Gravis ◽

Quality Of Life Scale ◽

Life Scale ◽

Translation And Validation

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UJI VALIDITAS DAN RELIABILITAS KUESIONER THE 15-ITEM MYASTHENIA GRAVIS QUALITY OF LIFE SCALE VERSI BAHASA INDONESIA (MG-QOL15 INA)

Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia ◽

10.52386/neurona.v37i4.176 ◽

2020 ◽

Vol 37 (4) ◽

Author(s):

Fitri Octaviana ◽

Ahmad Yanuar Safri ◽

Fikry Syahrial ◽

Luh Ari Indrawati ◽

Winnugroho Wiratman ◽

...

Keyword(s):

Quality Of Life ◽

Myasthenia Gravis ◽

World Health Organization ◽

World Health ◽

Quality Of Life Scale ◽

Life Scale ◽

Health Organization ◽

Bahasa Indonesia

Pendahuluan: Miastenia gravis (MG) merupakan penyakit autoimun kronik pada taut neuromuskular dengan gejala kelemahan fluktuatif. Kemajuan dalam diagnosis dan tatalaksana kasus MG akan meningkatkan angka harapan hidup pasien, sehingga evaluasi keberhasilan terapi tidak lagi hanya didasarkan pada mengatasi gejala, namun juga dalam mengevaluasi kualitas hidup pasien. The 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15) merupakan kuesioner yang digunakan saat ini untuk mengevaluasi kualitas hidup pada pasien MG. Tujuan: Mendapatkan instrumen MG-QOL15 versi bahasa Indonesia yang valid dan reliabel. Metode: Empat puluh empat pasien penyakit MG di Poliklinik Neurologi Rumah Sakit Cipto Mangunkusumo yang memenuhi kriteria inklusi diikutsertakan dalam penelitian potong lintang ini. Pasien mengisi kuesioner MG-QOL15 sebanyak 2 kali dengan jarak waktu 2 hari. Konsep yang digunakan untuk uji validitas MG-QOL15 INA adalah validasi lintas budaya menurut metode World Health Organization (WHO). Uji reliabilitas dinilai menggunakan nilai alfa Cronbach. Hasil: MG-QOL15 INA telah melalui validasi lintas budaya menurut WHO dengan nilai koefisien korelasi Spearman berkisar antara 0,568-0,789 pada pemeriksaan pertama dan 0,574-0,763 pada retest. Nilai alfa Cronbach pada pemeriksaan pertama 0,917 dan 0,909 untuk re-test. Diskusi: MG-QOL15 INA valid dan reliabel untuk digunakan sebagai instrumen evaluasi kualitas hidup pasien MG. Kata Kunci: MG-QOL15, Miastenia gravis, kualitas hidup

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Translation, cross-cultural adaptation, and validation of the french version of the 15-item Myasthenia Gravis Quality Of life scale

Muscle & Nerve ◽

10.1002/mus.25381 ◽

2017 ◽

Vol 55 (5) ◽

pp. 639-645 ◽

Cited By ~ 7

Author(s):

Simone Birnbaum ◽

Idir Ghout ◽

Sophie Demeret ◽

Francis Bolgert ◽

Bruno Eymard ◽

...

Keyword(s):

Quality Of Life ◽

Myasthenia Gravis ◽

Cultural Adaptation ◽

Cross Cultural ◽

Cross Cultural Adaptation ◽

French Version ◽

Quality Of Life Scale ◽

Life Scale

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Safety and tolerability of olanzapine compared with other antipsychotics in the treatment of elderly patients with schizophrenia: a naturalistic study

European Psychiatry ◽

10.1016/j.eurpsy.2004.06.008 ◽

2004 ◽

Vol 19 (6) ◽

pp. 358-365 ◽

Cited By ~ 11

Author(s):

Antonio Ciudad ◽

José-Manuel Montes ◽

José-Manuel Olivares ◽

Juan-Carlos Gómez ◽

Keyword(s):

Quality Of Life ◽

Adverse Events ◽

Elderly Patients ◽

Clinical Status ◽

Severity Of Illness ◽

Anticholinergic Drugs ◽

Naturalistic Study ◽

Quality Of Life Scale ◽

Life Scale

AbstractObjectiveTo evaluate the safety and tolerability of olanzapine in the treatment of elderly patients with schizophrenia.MethodsA total of 135 outpatients with schizophrenia ≥60 years of age were treated with olanzapine (n = 105) or another antipsychotic (n = 30) and followed up for 6 months. Safety measures included the recording of spontaneous adverse events and extrapyramidal symptoms (EPS). Clinical status and effectiveness of the medications were measured using the Clinical Global Impressions-Severity of Illness and the Global Assessment of Function (GAF) scales. Quality of life was assessed by means of the Spanish version of the EuroQol. The Awad scale was applied to evaluate patients’ subjective attitude towards medication.ResultsThe incidence of overall adverse events and EPS was non-significantly lower in patients treated with olanzapine than in patients treated with other antipsychotics. The use of anticholinergic drugs was significantly lower (P = 0.04) in patients treated with olanzapine. Both groups of patients experienced similar improvements in Clinical Global Impressions-Severity and GAF scores. Non-significantly greater improvement in the acceptance of medication occurred at endpoint in olanzapine-treated patients than in control patients as measured by the Awad scale. The improvement in the EuroQol quality of life scale achieved at the end of study did not differ between both treatment groups.ConclusionsResults from this naturalistic study showed that olanzapine was as safe and effective as other antipsychotic drugs in the treatment of elderly patients with schizophrenia.

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