Hiding in plain sight: The magnitude of unused disease modifying therapies in multiple sclerosis and strategies for reducing the economic burden of care

Administration USDoHaHSUSFD. Disposal of unused medicines: what you should know [online]. Available at: https://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/ucm186187.htm. Accessed 07/27/2018. Amezcua, 2021, Health disparities, inequities, and social determinants of health in multiple sclerosis and related disorders in the US: a review, JAMA Neurol., 78, 1515, 10.1001/jamaneurol.2021.3416 Bean, 2018, Pharmaceuticals in water, fish and osprey nestlings in Delaware river and bay, Environ. Pollut., 232, 533, 10.1016/j.envpol.2017.09.083 Caldito, 2018, Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study, Brain, 141, 3115, 10.1093/brain/awy245 Callaghan, 2019, Out-of-pocket costs are on the rise for commonly prescribed neurologic medications, Neurology, 92, e2604, 10.1212/WNL.0000000000007564 Chen, 2017, Multiple sclerosis: frequency, cost, and economic burden in the United States, J. Clin. Neurosci., 45, 180, 10.1016/j.jocn.2017.06.005 Cohen, 2010, Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis, N. Engl. J. Med., 362, 402, 10.1056/NEJMoa0907839 Cohen, 2012, Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial, Lancet, 380, 1819, 10.1016/S0140-6736(12)61769-3 Cohen, 2016, Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial, Lancet Neurol., 15, 373, 10.1016/S1474-4422(16)00018-1 Coles, 2012, Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial, Lancet, 380, 1829, 10.1016/S0140-6736(12)61768-1 Comi, 2011, Phase III dose-comparison study of glatiramer acetate for multiple sclerosis, Ann. Neurol., 69, 75, 10.1002/ana.22316 Confavreux, 2014, Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet Neurol., 13, 247, 10.1016/S1474-4422(13)70308-9 Daughton, 1999, Pharmaceuticals and personal care products in the environment: agents of subtle change?, Environ. Health Perspect., 107, 907, 10.1289/ehp.99107s6907 Giovannoni, 2010, A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis, N. Engl. J. Med., 362, 416, 10.1056/NEJMoa0902533 Hartung, 2015, The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: too big to fail?, Neurology, 84, 2185, 10.1212/WNL.0000000000001608 Hartung, 2017, Economics and cost-effectiveness of multiple sclerosis therapies in the USA, Neurotherapeutics, 14, 1018, 10.1007/s13311-017-0566-3 Hartung, 2021, Health economics of disease-modifying therapy for multiple sclerosis in the United States, Ther. Adv. Neurol. Disord., 14, 10.1177/1756286420987031 Hauser, 2017, Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis, N. Engl. J. Med., 376, 221, 10.1056/NEJMoa1601277 Hauser, 2020, Ofatumumab versus teriflunomide in multiple sclerosis, N. Engl. J. Med., 383, 546, 10.1056/NEJMoa1917246 Hincapie, 2017, Factors Associated with patient preferences for disease-modifying therapies in multiple sclerosis, J. Manag. Care Spec. Pharm., 23, 822 Hua, 2018, Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60, Mult. Scler., 25, 699, 10.1177/1352458518765656 Jacobs, 2000, Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS study group, N. Engl. J. Med., 343, 898, 10.1056/NEJM200009283431301 Johnson, 1995, Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group, Neurology, 45, 1268, 10.1212/WNL.45.7.1268 Kantarci, 2005, Natural history of multiple sclerosis, Neurol. Clin., 23, 17, 10.1016/j.ncl.2004.10.002 Kappos, 2015, Daclizumab HYP versus interferon beta-1a in relapsing multiple sclerosis, N. Engl. J. Med., 373, 1418, 10.1056/NEJMoa1501481 Khan, 2015, Multiple sclerosis in US minority populations: clinical practice insights, Neurol. Clin. Pract., 5, 132, 10.1212/CPJ.0000000000000112 Kister, 2010, Rapid disease course in African Americans with multiple sclerosis, Neurology, 75, 217, 10.1212/WNL.0b013e3181e8e72a Lublin, 2014, Defining the clinical course of multiple sclerosis: the 2013 revisions, Neurology, 83, 278, 10.1212/WNL.0000000000000560 Miller, 2014, Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet Neurol., 13, 977, 10.1016/S1474-4422(14)70191-7 Montalban, 2017, Ocrelizumab versus placebo in primary progressive multiple sclerosis, N. Engl. J. Med., 376, 209, 10.1056/NEJMoa1606468 Naismith, 2006, Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review, Mult. Scler., 12, 775, 10.1177/1352458506070923 O'Connor, 2011, Randomized trial of oral teriflunomide for relapsing multiple sclerosis, N. Engl. J. Med., 365, 1293, 10.1056/NEJMoa1014656 Rae-Grant, 2018, Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the american academy of neurology, Neurology, 90, 777, 10.1212/WNL.0000000000005347 Santos, 2010, Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment, J. Hazard. Mater., 175, 45, 10.1016/j.jhazmat.2009.10.100 Setayeshgar, 2018, Persistence and adherence to the new oral disease-modifying therapies for multiple sclerosis: a population-based study, Mult. Scler. Relat. Disord., 27, 364, 10.1016/j.msard.2018.11.004 1993, Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group, Neurology, 43, 655, 10.1212/WNL.43.4.655 Thompson, 2018, Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria, Lancet Neurol., 17, 162, 10.1016/S1474-4422(17)30470-2 Wallin, 2019, The prevalence of MS in the United States: a population-based estimate using health claims data, Neurology, 92, e1029, 10.1212/WNL.0000000000007035 Weinstock-Guttman, 2010, Increased tissue damage and lesion volumes in African Americans with multiple sclerosis, Neurology, 74, 538, 10.1212/WNL.0b013e3181cff6fb Zeydan, 2019, MS progression is predominantly driven by age-related mechanisms - commentary, Mult. Scler., 25, 906, 10.1177/1352458518824767