Browsing by Author "Dyck, P. James B."
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- Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosisPublication . Coelho, Teresa; Yarlas, Aaron; Waddington-Cruz, Marcia; White, Michelle K.; Sikora Kessler, Asia; Lovley, Andrew; Pollock, Michael; Guthrie, Spencer; Ackermann, Elizabeth J.; Hughes, Steven G.; Karam, Chafic; Khella, Sami; Gertz, Morie; Merlini, Giampaolo; Obici, Laura; Schmidt, Hartmut H.; Polydefkis, Michael; Dyck, P. James B.; Brannagan III, Thomas H.; Conceição, Isabel; Benson, Merrill D.; Berk, John L.Objective: To examine the impact on quality of life (QOL) of patients with hATTR amyloidosis with polyneuropathy treated with inotersen (Tegsedi™) versus placebo. Methods: Data were from the NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398), a phase 3, multinational, randomized, double-blind, placebo-controlled study of inotersen in patients with hATTR amyloidosis with polyneuropathy. At baseline and week 66, QOL measures-the Norfolk-QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2® Health Survey (SF-36v2)-were assessed. Treatment differences in mean changes in QOL from baseline to week 66 were tested using mixed-effect models with repeated measures. Responder analyses compared the percentages of patients whose QOL meaningfully improved or worsened from baseline to week 66 in inotersen and placebo arms. Descriptive analysis of item responses examined treatment differences in specific activities and functions at week 66. Results: Statistically significant mean differences between treatment arms were observed for three of five Norfolk-QOL-DN domains and five of eight SF-36v2 domains, with better outcomes for inotersen than placebo in physical functioning, activities of daily living, neuropathic symptoms, pain, role limitations due to health problems, and social functioning. A larger percentage of patients in the inotersen arm than the placebo arm showed preservation or improvement in Norfolk-QOL-DN and SF-36v2 scores from baseline to week 66. Responses at week 66 showed more substantial problems with daily activities and functioning for patients in the placebo arm than in the inotersen arm. Conclusion: Patients with hATTR amyloidosis with polyneuropathy treated with inotersen showed preserved or improved QOL at 66 weeks compared to those who received placebo.
- Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosisPublication . Dyck, P. James B.; Coelho, Teresa; Waddington Cruz, Marcia; Brannagan, Thomas H.; Khella, Sami; Karam, Chafic; Berk, John L.; Polydefkis, Michael J.; Kincaid, John C.; Wiesman, Janice F.; Litchy, William J.; Mauermann, Michelle L.; Ackermann, Elizabeth J.; Baker, Brenda F.; Jung, Shiangtung W.; Guthrie, Spencer; Pollock, Michael; Dyck, Peter J.Introduction: Hereditary transthyretin-mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO-TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients' neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score. Methods: Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks. Results: At 66 weeks, inotersen-treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items. Discussion: Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients' neuropathy experience in clinical practice.