Browsing by Author "Freimer, Miriam L."

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    Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study
    (Wolters Kluwer, 2021-10-18) Wencel, Marie; Shaibani, Aziz; Goyal, Namita A.; Dimachkie, Mazen M.; Trivedi, Jaya; Johnson, Nicholas E.; Gutmann, Laurie; Wicklund, Matthew P.; Bandyopadhay, Sankar; Genge, Angela L.; Freimer, Miriam L.; Goyal, Neelam; Pestronk, Alan; Florence, Julaine; Karam, Chafic; Ralph, Jeffrey W.; Rasheed, Zinah; Hays, Melissa; Hopkins, Steve; Mozaffar, Tahseen; Neurology, School of Medicine
    Background and objectives: We investigated the prevalence of late-onset Pompe disease (LOPD) in patients presenting to 13 academic, tertiary neuromuscular practices in the United States and Canada. Methods: All successive patients presenting with proximal muscle weakness or isolated hyperCKemia and/or neck muscle weakness to these 13 centers were invited to participate in the study. Whole blood was tested for acid alpha-glucosidase (GAA) assay through the fluorometric method, and all cases with enzyme levels of ≤10 pmoL/punch/h were reflexed to molecular testing for mutations in the GAA gene. Clinical and demographic information was abstracted from their clinical visit and, along with study data, entered into a purpose-built REDCap database, and analyzed at the University of California, Irvine. Results: GAA enzyme assay results were available on 906 of the 921 participants who consented for the study. LOPD was confirmed in 9 participants (1% prevalence). Another 9 (1%) were determined to have pseudodeficiency of GAA, whereas 19 (1.9%) were found to be heterozygous for a pathogenic GAA mutation (carriers). Of the definite LOPD participants, 8 (89%) were Caucasian and were heterozygous for the common leaky (IVS1) splice site mutation in the GAA gene (c -32-13T>G), with a second mutation that was previously confirmed to be pathogenic. Discussion: The prevalence of LOPD in undiagnosed patients meeting the criteria of proximal muscle weakness, high creatine kinase, and/or neck weakness in academic, tertiary neuromuscular practices in the United States and Canada is estimated to be 1%, with an equal prevalence rate of pseudodeficiency alleles.
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    Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study
    (Wolters Kluwer, 2022-01-25) Nowak, Richard J.; Coffey, Christopher S.; Goldstein, Jonathan M.; Dimachkie, Mazen M.; Benatar, Michael; Kissel, John T.; Wolfe, Gil I.; Burns, Ted M.; Freimer, Miriam L.; Nations, Sharon; Granit, Volkan; Smith, A. Gordon; Richman, David P.; Ciafaloni, Emma; Al-Lozi, Muhammad T.; Sams, Laura Ann; Quan, Dianna; Ubogu, Eroboghene; Pearson, Brenda; Sharma, Aditi; Yankey, Jon W.; Uribe, Liz; Shy, Michael; Amato, Anthony A.; Conwit, Robin; O'Connor, Kevin C.; Hafler, David A.; Cudkowicz, Merit E.; Barohn, Richard J.; NeuroNEXT NN103 BeatMG Study Team; Neurology, School of Medicine
    Objective: To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). Methods: The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks. Results: Of the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs. 56% on placebo. The study reached its futility endpoint (p=0.03) suggesting that the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified. Conclusions: While rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase-3 trial of mild-moderately symptomatic AChR-Ab+ gMG. Classification of evidence: This study provides Class I evidence that for mild-to-moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.