کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8343049 | 1541547 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5â¯years of treatment
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کلمات کلیدی
tmaxNaBSAETABMVVAUCinfVDZMedDRASMQHAQN-acetylgalactosamine-6-sulfataselong-term extensionMorquio Amucopolysaccharidosis IVACmaxFEV1IgEVDSSFVCelosulfase alfa6-min walk test - 6 دقیقه پیاده روی تست6MWT - 6 مگاواتt1/2 - t1 / 2Neutralizing antibodies - آنتی بادیهای ناتریالenzyme replacement therapy - آنزیم جایگزین درمانImmunoglobulin E - ایمونوگلوبولین Eclearance - ترخیص کالا از گمرکforced expiratory volume in 1 s - حجم انبساط اجباری در 1 ثانیهvolume of distribution at steady state - حجم توزیع در حالت پایدارMaximum voluntary ventilation - حداکثر تهویه داوطلبانهIntravenous - داخل وریدیMedical Dictionary for Regulatory Activities - دیکشنری پزشکی برای فعالیت های نظارتیtime to reach Cmax - زمان برای رسیدن به CmaxGALNS - سرماخوردگیKeratan sulfate - سولفات برشforced vital capacity - ظرفیت حیاتی اجباریadverse event - عارضه جانبی یا عوارض جانبیSerious adverse event - عوارض جانبی جدیPharmacodynamics - فارماکودینامیکPharmacokinetics - فارماکوکینتیکMucopolysaccharidosis - موکوپلیساکاریدوزMPs - نمایندگان مجلسterminal half-life - نیمه عمر پایانیERT - هستندInfusion reaction - واکنش تزریقHealth Assessment Questionnaire - پرسشنامه ارزیابی سلامتcation-independent mannose 6-phosphate receptor - گیرنده 6-فسفات مانوز مستقل وابسته به کاتیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Elosulfase alfa is an enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis IVA), a multisystemic progressive lysosomal storage disorder. This report includes the primary treatment outcomes and immunogenicity profile of elosulfase alfa in patients with Morquio A syndrome from 2 sequential studies, MOR-002 (ClinicalTrials.govNCT00884949) and MOR-100 (NCT01242111), representing >5â¯years of clinical study data. MOR-002 was an open-label, single-arm phase 1/2 study that evaluated the pharmacokinetics, safety, immunogenicity, and preliminary efficacy of 3 sequential doses of elosulfase alfa (0.1, 1.0, and 2.0â¯mg/kg/week) in patients with Morquio A syndrome (nâ¯=â¯20) over 36â¯weeks, followed by an optional 36- to 48-week treatment period using elosulfase alfa 1.0â¯mg/kg once weekly (qw). During the 0.1â¯mg/kg dosing phase, 1 patient discontinued due to a type I hypersensitivity adverse event (AE), and that patient's sibling voluntarily discontinued in the absence of AEs. An additional patient discontinued due to recurrent infusion reactions during the 1.0â¯mg/kg continuation phase. The remaining 17 patients completed MOR-002 and enrolled in MOR-100, an open-label, long-term extension study that further evaluated safety and clinical outcomes with elosulfase alfa administered at 2.0â¯mg/kg qw. During the course of MOR-100, patients were given the option of receiving elosulfase alfa infusions at home with nursing assistance. Over the course of both studies, all patients experienced â¥1 AE and most patients experienced a drug-related AE, generally of mild or moderate severity. Hypersensitivity reactions reported as related to study drug occurred in 25% of patients. Thirteen patients who chose to receive infusions at home had the same tolerability and safety profile, as well as comparable compliance rates, as patients who chose to receive on-site infusions. All patients developed antibodies to elosulfase alfa. Positivity for neutralizing antibodies was associated with increased drug half-life and decreased drug clearance. Despite formation of antidrug-binding (total antidrug antibodies, TAb) and in vitro neutralizing antibodies (NAb) in all patients, these types of immunogenicity to elosulfase alfa were not correlated with safety or clinical outcomes. In contrast with the reported natural history of Morquio A, no trends toward decreasing endurance, respiratory function, or ability to perform activities of daily living were observed in this cohort over the 5-year period.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 123, Issue 4, April 2018, Pages 479-487
Journal: Molecular Genetics and Metabolism - Volume 123, Issue 4, April 2018, Pages 479-487
نویسندگان
Christian Hendriksz, Saikat Santra, Simon A. Jones, Tarekegn Geberhiwot, Lynne Jesaitis, Brian Long, Yulan Qi, Sara M. Hawley, Celeste Decker,