Browsing by Author "Gertz, Morie A."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Burden of hereditary transthyretin amyloidosis on quality of life
    (Wiley, 2019-08) Yarlas, Aaron; Gertz, Morie A.; Dasgupta, Noel R.; Obici, Laura; Pollock, Michael; Ackermann, Elizabeth J.; Lovley, Andrew; Kessler, Asia Sikora; Patel, Pankaj A.; White, Michelle K.; Guthrie, Spencer D.; Medicine, School of Medicine
    INTRODUCTION: Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL). METHODS: Neuropathy-specific QOL, measured with the Norfolk QOL-Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36-item Short Form Health Survey version 2 (SF-36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases. RESULTS: Neuropathy-specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure. DISCUSSION: Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169-175, 2019
  • Thumbnail Image
    Item
    Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen
    (Springer, 2023) Coelho, Teresa; Waddington Cruz, Márcia; Chao, Chi-Chao; Parman, Yeşim; Wixner, Jonas; Weiler, Markus; Barroso, Fabio A.; Dasgupta, Noel R.; Jung, Shiangtung W.; Schneider, Eugene; Viney, Nicholas J.; Dyck, P. James B.; Ando, Yukio; Gillmore, Julian D.; Khella, Sami; Gertz, Morie A.; Obici, Laura; Berk, John L.; Medicine, School of Medicine
    Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study. Methods: Patients eligible for NEURO-TTRansform were 18-82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II. Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0. Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice.
  • Thumbnail Image
    Item
    Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial
    (Taylor & Francis, 2018-07-03) Waddington-Cruz, Marcia; Ackermann, Elizabeth J.; Polydefkis, Michael; Heitner, Stephen B.; Dyck, Peter J.; Barroso, Fabio A.; Wang, Annabel K.; Berk, John L.; Dyck, P. James B.; Monia, Brett P.; Hughes, Steven G.; Tai, Li; Kwoh, T. Jesse; Jung, Shiangtung W.; Coelho, Teresa; Benson, Merrill D.; Gertz, Morie A.; Pathology and Laboratory Medicine, School of Medicine
    Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations.Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis.Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed.Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity.Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.
  • Thumbnail Image
    Item
    In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs
    (Elsevier, 2015-08) Tefferi, Ayalew; Kantarjian, Hagop; Rajkumar, S. Vincent; Baker, Lawrence H.; Abkowitz, Jan L.; Adamson, John W.; Advani, Ranjana Hira; Allison, James; Antman, Karen H.; Bast Jr., Robert C.; Bennett, John M.; Benz Jr., Edward J.; Berliner, Nancy; Bertino, Joseph; Bhatia, Ravi; Bhatia, Smita; Bhojwani, Deepa; Blanke, Charles D.; Bloomfield, Clara D.; Bosserman, Linda; Broxmeyer, Hal E.; Byrd, John C.; Cabanillas, Fernando; Canellos, George Peter; Chabner, Bruce A.; Chanan-Khan, Asher; Cheson, Bruce; Clarkson, Bayard; Cohn, Susan L.; Colon-Otero, Gerardo; Cortese, Jorge; Coutre, Steven; Cristofanilli, Massimo; Curran Jr., Walter J.; Daley, George Q.; DeAngelo, Daniel J.; Deeg, H. Joachim; Einhorn, Lawrence H.; Erba, Harry P.; Esteva, Francisco J.; Estey, Elihu; Fidler, Isaiah J.; Foran, James; Forman, Stephen; Freireich, Emil; Fuchs, Charles; George, James N.; Gertz, Morie A.; Giralt, Sergio; Golomb, Harvey; Greenberg, Peter; Gutterman, Jordan; Handin, Robert I.; Hellman, Samuel; Hoff, Paulo Marcelo; Hoffman, Ronald; Hong, Waun Ki; Horowitz, Mary; Hortobagyi, Gabriel N.; Hudis, Clifford; Issa, Jean Pierre; Johnson, Bruce Evan; Kantoff, Philip W.; Kaushansky, Kenneth; Khayat, David; Khuri, Fadlo R.; Kipps, Thomas J.; Kripke, Margaret; Kyle, Robert A.; Larson, Richard A.; Lawrence, Theodore S.; Levine, Ross; Link, Michael P.; Lippman, Scott M.; Lonial, Sagar; Lyman, Gary H.; Markman, Maurie; Mendelsohn, John; Meropol, Neal J.; Messinger, Yoav; Mulvey, Therese M.; O’Brien, Susan; Perez-Soler, Roman; Pollock, Raphael; Prchal, Josef; Press, Oliver; Radich, Jerald; Rai, Kanti; Rosenberg, Saul A.; Rowe, Jacob M.; Rugo, Hope; Runowicz, Carolyn D.; Sandmaier, Brenda M.; Saven, Alan; Schafer, Andrew I.; Schiffer, Charles; Sekeres, Mikkael A.; Silver, Richard T.; Siu, Lillian L.; Steensma, David P.; Stewart, F. Marc; Stock, Wendy; Stone, Richard; Storb, Rainer; Strong, Louise C.; Tallman, Martin S.; Thompson, Michael; Ueno, Naoto T.; Van Etten, Richard A.; Vose, Julie M.; Wiernik, Peter H.; Winer, Eric P.; Younes, Anas; Zelenetz, Andrew D.; Department of Medicine, IU School of Medicine
    Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015]
  • Thumbnail Image
    Item
    Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis
    (MMS, 2018-07) Benson, Merrill D.; Waddington-Cruz, Márcia; Berk, John L.; Polydefkis, Michael; Dyck, Peter J.; Wang, Annabel K.; Planté-Bordeneuve, Violaine; Barroso, Fabio A.; Merlini, Giampaolo; Obici, Laura; Scheinberg, Morton; Brannagan, Thomas H., III; Litchy, William J.; Whelan, Carol; Drachman, Brian M.; Adams, David; Heitner, Stephen B.; Conceição, Isabel; Schmidt, Hartmut H.; Vita, Giuseppe; Campistol, Josep M.; Gamez, Josep; Gorevic, Peter D.; Gane, Edward; Shah, Amil M.; Solomon, Scott D.; Monia, Brett P.; Hughes, Steven G.; Kwoh, Jesse; McEvoy, Bradley W.; Jung, Shiangtung W.; Baker, Brenda F.; Ackermann, Elizabeth J.; Gertz, Morie A.; Coelho, Teresa; Pathology and Laboratory Medicine, School of Medicine
    BACKGROUND Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin (TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2′-O-methoxyethyl–modified antisense oligonucleotide, inhibits hepatic production of transthyretin. METHODS We conducted an international, randomized, double-blind, placebo-controlled, 15-month, phase 3 trial of inotersen in adults with stage 1 (patient is ambulatory) or stage 2 (patient is ambulatory with assistance) hereditary transthyretin amyloidosis with polyneuropathy. Patients were randomly assigned, in a 2:1 ratio, to receive weekly subcutaneous injections of inotersen (300 mg) or placebo. The primary end points were the change in the modified Neuropathy Impairment Score+7 (mNIS+7; range, −22.3 to 346.3, with higher scores indicating poorer function; minimal clinically meaningful change, 2 points) and the change in the score on the patient-reported Norfolk Quality of Life–Diabetic Neuropathy (QOL-DN) questionnaire (range, −4 to 136, with higher scores indicating poorer quality of life). A decrease in scores indicated improvement. RESULTS A total of 172 patients (112 in the inotersen group and 60 in the placebo group) received at least one dose of a trial regimen, and 139 (81%) completed the intervention period. Both primary efficacy assessments favored inotersen: the difference in the least-squares mean change from baseline to week 66 between the two groups (inotersen minus placebo) was −19.7 points (95% confidence interval [CI], −26.4 to −13.0; P<0.001) for the mNIS+7 and −11.7 points (95% CI, −18.3 to −5.1; P<0.001) for the Norfolk QOL-DN score. These improvements were independent of disease stage, mutation type, or the presence of cardiomyopathy. There were five deaths in the inotersen group and none in the placebo group. The most frequent serious adverse events in the inotersen group were glomerulonephritis (in 3 patients [3%]) and thrombocytopenia (in 3 patients [3%]), with one death associated with one of the cases of grade 4 thrombocytopenia. Thereafter, all patients received enhanced monitoring. CONCLUSIONS Inotersen improved the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis. Thrombocytopenia and glomerulonephritis were managed with enhanced monitoring.