title: Predictors of long-term interferon discontinuation in newly diagnosed relapsing multiple sclerosis.
abstract: BACKGROUND
  Interferon-β has long-term safety and efficacy profiles for Relapsing Remitting Multiple Sclerosis (RRMS). However, the increasing number of available treatments requires to improve patient profiling and to perform individualized clinical decisions. Therefore, the present study investigated predictors of Interferon-β discontinuation.
  
  
  METHODS
  The present retrospective observational cohort study included 499 newly diagnosed, drug naïve RRMS subjects receiving Interferon-β as first disease modifying treatment (DMT), during a 7.9±3.8 year period, up to treatment discontinuation. Possible markers of interest were recorded at the time of diagnosis (age, gender, disease duration, baseline EDSS) or during follow-up as variables of disease evolution (relapse occurrence, annualized relapse rate -ARR-, 1-point EDSS progression, reaching of EDSS 4.0) or of treatment (high-dose Interferon-β1a, low-dose Interferon-β1a, or Interferon-β1b).
  
  
  RESULTS
  217 patients (43.5%) discontinued the treatment during the follow-up period, with an incidence of 5% person-years (95%CI=4.6-5.9%). A multivariate Cox regression model showed an increased rate of Interferon-β discontinuation for female gender (p=0.019; HR=1.428), higher baseline EDSS (p=0.026; HR=1.346), relapse occurrence (p=0.009; HR=1.618), higher ARR (p<0.001; HR=5.269), and Interferon-β1b treatment (p=0.019; HR=1.506); and a reduced rate for occurrence of EDSS progression (p<0.001; HR=0.299).
  
  
  CONCLUSIONS
  Most of the factors associated with Interferon-β discontinuation are not modifiable, and are part of demographic features (i.e. gender), or of disease characteristics (i.e. disability at diagnosis), but should be taken into account when prescribing the first DMT for MS. Noteworthy, the use of Interferon-β1b is associated with 50% increased risk of discontinuation, compared with high-dose Interferon-β1a, highlighting the importance of drug formulations in treatment persistence.
authors.affiliation: Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy. Electronic address: moccia.marcello@gmail.com.
authors.forename: Marcello
authors.initials: M
authors.lastname: Moccia
authors.affiliation: Department of Primary Care and Public Health, Imperial College, London, UK; Department of Public Health, Federico II University, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palladino
authors.affiliation: Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carotenuto
authors.affiliation: Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Cinzia Valeria
authors.initials: CV
authors.lastname: Russo
authors.affiliation: Department of Public Health, Federico II University, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Triassi
authors.affiliation: Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lanzillo
authors.affiliation: Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brescia Morra
mesh_terms: D000328:Adult; D000367:Age Factors; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D015994:Incidence; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D000068576:Interferon beta-1b / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D055118:Medication Adherence; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D007155:Immunologic Factors; D000068576:Interferon beta-1b; D000068556:Interferon beta-1a
keywords: Discontinuation; Interferon; Longitudinal; Multiple sclerosis; Persistence