title: Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis.
abstract: OBJECTIVE
  To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.
  
  
  METHODS
  Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.
  
  
  RESULTS
  Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.
  
  
  CONCLUSIONS
  Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.
authors.affiliation: Departments of Medicine and Neurology, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. tomas.kalincik@unimelb.edu.au
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Timothy
authors.initials: T
authors.lastname: Spelman
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Edgardo
authors.initials: E
authors.lastname: Cristiano
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'maison
authors.forename: Daniele
authors.initials: D
authors.lastname: La Spitaleri
authors.forename: Maria Edite
authors.initials: ME
authors.lastname: Rio
authors.forename: Sholmo
authors.initials: S
authors.lastname: Flechter
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giuliani
authors.forename: Aldo
authors.initials: A
authors.lastname: Savino
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez-Bolanos
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Norma
authors.initials: N
authors.lastname: Deri
authors.forename: Orla
authors.initials: O
authors.lastname: Gray
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.forename: Marcela
authors.initials: M
authors.lastname: Fiol
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.forename: Erik
authors.initials: E
authors.lastname: van Munster
authors.forename: Vetere
authors.initials: V
authors.lastname: Santiago
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Saladino
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.forename: Cameron
authors.initials: C
authors.lastname: Shaw
authors.forename: Krisztian
authors.initials: K
authors.lastname: Kasa
authors.forename: Tatjana
authors.initials: T
authors.lastname: Petkovska-Boskova
authors.forename: Leontien
authors.initials: L
authors.lastname: den Braber-Moerland
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.forename: Eli
authors.initials: E
authors.lastname: Skromne
authors.forename: Joseph
authors.initials: J
authors.lastname: Herbert
authors.forename: Dieter
authors.initials: D
authors.lastname: Poehlau
authors.forename: Merrilee
authors.initials: M
authors.lastname: Needham
authors.forename: Elizabeth Alejandra Bacile
authors.initials: EA
authors.lastname: Bacile
authors.forename: Walter Oleschko
authors.initials: WO
authors.lastname: Arruda
authors.forename: Mark
authors.initials: M
authors.lastname: Paine
authors.forename: Bhim
authors.initials: B
authors.lastname: Singhal
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cabrera-Gomez
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D008297:Male; D055118:Medication Adherence; D009103:Multiple Sclerosis / Q000188:drug therapy*; D057216:Propensity Score; D015203:Reproducibility of Results; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D016899:Interferon-beta; D000068556:Interferon beta-1a