title: Impact of exposure to interferon beta-1a on outcomes in patients with relapsing-remitting multiple sclerosis: exploratory analyses from the PRISMS long-term follow-up study.
abstract: OBJECTIVE
  To explore the effects of exposure to subcutaneous (sc) interferon (IFN) beta-1a on efficacy in patients with relapsing-remitting multiple sclerosis (RRMS) enrolled in the PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study.
  
  
  METHODS
  Patients with RRMS received IFN beta-1a, 44 or 22 µg sc three times weekly (tiw), or placebo, for 2 years, at which point placebo recipients were re-randomized to IFN beta-1a, 44 or 22 µg sc tiw, for a further 2-4 years. Long-term follow-up visits occurred 7-8 years after enrolment and allowed participation of patients who had previously discontinued treatment. Post hoc descriptive analyses were conducted within the lower (MIN) and upper (MAX) quartiles of patients divided according to cumulative dose of IFN beta-1a and cumulative time on treatment. Outcomes were explored in patients initially randomized to IFN beta-1a, 44 µg sc tiw, who had received continuous or noncontinuous therapy during the study.
  
  
  RESULTS
  For both cumulative dose and time analyses, the MIN and MAX groups comprised 96 and 95 patients, respectively. The continuous and noncontinuous groups included 45 and 91 patients, respectively. The MAX DOSE and MAX TIME groups had lower annualized relapse rates, lower rates of conversion to secondary progressive MS, lower percentages of patients with Expanded Disability Status Scale progression, higher percentages of relapse-free patients, and less T2 burden of disease than the MIN groups. The continuous therapy group had a lower annualized relapse rate and lower percentages of patients with Expanded Disability Status Scale progression or conversion to secondary progressive MS than the noncontinuous therapy group.
  
  
  CONCLUSIONS
  The findings of these post hoc analyses suggest that high exposure to sc IFN beta-1a may be associated with better clinical outcomes than low exposure, and also highlight the importance of maximizing adherence. Additional prospective investigation is warranted to evaluate further the effects of treatment exposure on outcomes and to determine the benefits of interventions to improve adherence.
authors.affiliation: MS Center, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Uitdehaag
authors.forename: Cris
authors.initials: C
authors.lastname: Constantinescu
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelisse
authors.forename: Douglas
authors.initials: D
authors.lastname: Jeffery
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.forename: Magnhild
authors.initials: M
authors.lastname: Sandberg-Wollheim
authors.forename: Anthony
authors.initials: A
authors.lastname: Traboulsee
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Verdun
authors.forename: Victor
authors.initials: V
authors.lastname: Rivera