Browsing by Author "Amato, Anthony A."

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    Long-term effect of thymectomy in patients with non-thymomatous myasthenia gravis treated with prednisone: 2-year extension of the MGTX randomised tria
    (Elsevier, 2019-03) Wolfe, Gil I.; Kaminski, Henry J.; Aban, Inmaculada B.; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J. Gabriel; Heckmann, Jeannine M.; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O.; Beydoun, Said R.; Chalk, Colin H.; Barboi, Alexandru C.; Amato, Anthony A.; Shaibani, Aziz I.; Katirji, Bashar; Lecky, Bryan R. F.; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T.; Rivner, Michael H.; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M.; Jackson, Carlayne E.; Verschuuren, Jan J. G. M.; Massey, Janice M.; Kissel, John T.; Werneck, Lineu C.; Benatar, Michael; Barohn, Richard J.; Tandan, Rup; Mozaffar, Tahseen; Silvestri, Nicholas J.; Conwit, Robin; Sonett, Joshua R.; Jaretzki, Alfred, III; Newsom-Davis, John; Cutter, Gary R.; Neurology, School of Medicine
    Background: The MGTX trial demonstrated that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status measured by the Quantitative MG (QMG) score in patients with non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: A multicentre, rater-blinded 2-year extension study was conducted across 36 centres in 15 countries for patients who completed the MGTX randomised, controlled trial and were willing to participate. MGTX trial patients were aged 18 to 65 years at enrollment, had generalised non-thymomatous myasthenia gravis (MG) with disease duration less than 5 years and elevated (≥1.00 nmol/l; 0.50–0.99 nmol/l allowed if confirmed by positive edrophonium or electrophysiologic testing) acetylcholine receptor antibody titers.. All patients received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints were the time-weighted average of both the QMG and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention-to-treat. The trial was registered on clinicaltrials.gov, number NCT00294658. Findings: Of 111 subjects who completed the 3-year MGTX trial, 68 (61%) entered the extension study between September 1, 2009 and August 26, 2015 (33 prednisone alone; 35 prednisone plus thymectomy). Of the 68, 50 (74%) completed the 60-month assessment (24 prednisone alone; 26 prednisone plus thymectomy). At 5 years, patients randomised to thymectomy plus prednisone continued to demonstrate improved clinical status compared to patients in the prednisone alone group based on time-weighted average QMG (5.47±3.87 vs. 9.34±5.08; 95% CI for the difference 0.71–7.04; p=0.0007) and lower average alternate-day prednisone requirements (24 mg±21 mg vs. 48±29 mg; 95% CI for the difference 12–36 mg; p=0.0002). The proportion of patients requiring hospitalisation for MG exacerbation (6% vs. 30%; 95% CI for the difference 7.1–42.1%; p=0.0105) was lower in the thymectomy group. Other MEDRA-coded adverse events were infrequent, occurring at a rate of ≤6% in both groups and did not differ significantly between them. There were no treatment-related deaths. Interpretation: After 5 years, thymectomy continues to confer benefits in generalised non-thymomatous MG. Although caution in predicting benefit for all such patients is appropriate since the extension study included only half of MGTX trial subjects, results available through month 60 provide further evidence to support thymectomy in this large group of patients with generalised MG.
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    Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
    (Wiley, 2022) Statland, Jeffrey M.; Campbell, Craig; Desai, Urvi; Karam, Chafic; Díaz-Manera, Jordi; Guptill, Jeffrey T.; Korngut, Lawrence; Genge, Angela; Tawil, Rabi N.; Elman, Lauren; Joyce, Nanette C.; Wagner, Kathryn R.; Manousakis, Georgios; Amato, Anthony A.; Butterfield, Russell J.; Shieh, Perry B.; Wicklund, Matthew; Gamez, Josep; Bodkin, Cynthia; Pestronk, Alan; Weihl, Conrad C.; Vilchez-Padilla, Juan J.; Johnson, Nicholas E.; Mathews, Katherine D.; Miller, Barry; Leneus, Ashley; Fowler, Marcie; van de Rijn, Marc; Attie, Kenneth M.; Neurology, School of Medicine
    Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. Methods: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated. Results: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P < .0001) and 9.5% (3.2%-15.9%) in the TA group (P = .01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection-site reactions. Discussion: Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements with up to 12 months of treatment.