Impact of new oral disease-modifying therapies on the prescription of injectable and off-label drugs in multiple sclerosis in France over 2011-2015 using national administrative databases
Résumé
Background: Multiple sclerosis (MS) is a chronic neurological disease starting in young adulthood and leading to disability on the long-term. Fifteen disease-modifying therapies (DMTs) specific for MS are available in France. Among these DMTs, six are injectable drugs (four beta-interferon, peginterferon and glatiramer acetate), three are in-hospital infused DMTs, and three are off-label drugs (azathioprine, methotrexate, and mycophenolate mofetil). From 2011 to 2015, three oral DMTs were introduced and widely prescribed: fingolimod (2011), teriflunomide (2014), and dimethyl fumarate (DMF) (2015).
Objectives: To describe the landscape of DMTs in France over the 2011-2015 period and evaluate the impact of oral drugs on the prescription of injectable and off-label DMTs.
Methods: An exhaustive study population was formed of the prevalent and incident persons with MS (PwMS) in the French national health insurance databases (97% of French population covered). They were identified over 2010-2015 thanks to a validated algorithm using diagnoses of hospital admissions, MS-specific DMTs and MS long disease duration status. Their care consumption, especially DMT prescription, was followed in the databases from January 1, 2011, until the earliest of death or December 31, 2015. For each category of DMT (injectable excluding peginterferon, off-label, and oral), the proportion of PwMS who used each DMT was computed annually and over all study period.
Results: In total, 111 334 PwMS, whom 56 122 (50.4%) had at least one delivery of a DMT, were identified in the databases, with a F:M sex-ratio of 2.5 and a median age of 47 years in 2011. Over 2011-2015, 40 721 (36.6%) and 8734 (7.8%) patients had at least one prescription of an injectable or off-label DMT, respectively. Since 2011, 23 062 patients (20.7%) had at least one delivery of an oral DMT, namely, 8912 had fingolimod, 8151 DMF, and 7206 teriflunomide. The proportion of PwMS using fingolimod rose from 0.1% to 6.7%, and teriflunomide from 1.5% to 6.4% over their respective availability period. DMF was used by 7.4% of PwMS its first year of availability. Conversely, use of injectable DMTs decreased from 24.8% to 19.3% and use of off-label DMTs remained stable around 4.5% over the study period.
Conclusions: This first study on the whole population of PwMS in France permitted to highlight the increasing prescription of oral DMTs since their introduction at the expense of injectable drugs.