Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

União homoafetiva : novo modelo de entidade familiar

Trata-se de jurisprudência comentada.Aborda as características relacionadas à concepção moderna de família e os núcleos familiares contemplados pelo direito brasileiro. Avalia a união homoafetiva à luz da ordem constitucional vigente, examinando a tutela estatal dessa forma de convívio. Destaca os efeitos jurídicos que decorrem da união afetiva homossexual, denotando que eles são adequados somente se a aludida união for reconhecida como unidade familiar

Fatores antinutricionais da casca e da polpa desidratada de café (Coffea arabica L.) armazenadas em diferentes períodos Antinutritional factors of the hull and dehydrated pulp of coffee (Coffea arabica L.) stored in different periods

Avaliaram-se os teores de cafeína, taninos, lignina e sílica, na casca e polpa de café das cultivares Catuaí, Rubi e Mundo Novo. A polpa foi obtida pela despolpa úmida em despolpador mecânico e, em seguida, seca ao sol até 13% de umidade. Os materiais foram armazenados em sacos de ráfia, em ambiente coberto, ventilado e seco, com amostragem em triplicata a cada 90 dias. A regressão mostrou aumento quadrático de 11,7% no teor de cafeína ao longo de 360 dias de armazenamento. O teor de taninos reduziu-se linearmente ao longo do armazenamento. Os valores de taninos foram de 1,70% comparado a 2,77% nos materiais sem armazenamento, redução de aproximadamente 38,6% no período de um ano. Os teores de lignina reduziram linearmente em 2,6% para a porcentagem de lignina na MS (11,7 para 11,4%) e 5,8% na porcentagem de lignina da FDN (10,4 para 9,8%), nos materiais sem armazenagem comparados a doze meses de armazenamento. Houve diferença significativa entre casca e polpa para a variável sílica. Maior valor de sílica na casca comparado à polpa pode ser decorrente da presença do pergaminho, uma vez que a polpa não o possui. A armazenagem da casca e polpa por um período de doze meses melhora as qualidades destes materiais, uma vez que reduziu os teores de taninos e lignina. Os teores de cafeína encontrados são limitantes na utilização de grandes quantidades desses materiais para ruminantes.<br>It was evaluated the caffeine contents of caffeine, tannins, lignin and silica in the hull and pulp of coffee of cultivars Catuaí, Rubi, Mundo Novo. Pulp was obtained by moist pulping in a mechanical pulper and dried in the sun adjusted to 13% moisture. Materials were stored in raffia bag in environment free of moisture and ventilated with samplings every 90 days. The quadratic effect shown increased caffeine content along 360 day storage, this increase was of 11,7% along 12 months. Tannin content was reduced linearly along the storage. The values of tannin were of 2.77% compared with 1.70% in the materials without storage. The reduction was of 38.6% in one year period. Lignin contents were reduced linearly in 2.6% for lignin percentage in DM (11.7 to 11.4%) and 5.8% in the lignin percentage of NDF (10.4 to 9.8%) in the materials with no storage compared to 12-month storage. There was a significant difference between the hull and pulp for the variable silica. Increased value of silica in the hull, compared to the pulp may be due to the presence of parchment in this material, since this pulp does no possess it. The storage of hull and pulp for a 12-month period improves the qualities of these materials since it reduced tannin and lignin contents. The values of caffeine found are limiting in the use of great amounts of those materials for ruminants

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis