title: A one-year prospective, randomized, placebo-controlled, quadruple-blinded, phase II safety pilot trial of combination therapy with interferon beta-1a and mycophenolate mofetil in early relapsing-remitting multiple sclerosis (TIME MS).
abstract: BACKGROUND
  Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor with immunomodulatory effects on B cells, T cells, and macrophages.
  
  
  OBJECTIVE
  To conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in combination with either placebo or oral MMF in multiple sclerosis (MS).
  
  
  METHODS
  Twenty-four treatment-naïve R-RMS patients participated in a one-year prospective, placebo-controlled, blinded, safety pilot clinical trial. Every patient injected weekly intramuscular interferon beta-1a. The cohort was then randomized (1 : 1) to either active oral MMF or identical-appearing placebo tablets. Clinical evaluations were assessed every 3 months, along with brain MRI scans performed at baseline and repeated every 60 days for one year. Comprehensive laboratory assessments were monitored for safety, along with adverse events.
  
  
  RESULTS
  In this small pilot investigation, no differences were identified between the two treatment groups with respect to patient-reported adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these observations, and the limited number of patients treated, trends appeared to favor the combination therapy regimen.
  
  
  CONCLUSIONS
  The combination treatment regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot study. Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of MMF in MS appears warranted.
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Remington
authors.forename: Katherine
authors.initials: K
authors.lastname: Treadaway
authors.forename: Teresa
authors.initials: T
authors.lastname: Frohman
authors.forename: Amber
authors.initials: A
authors.lastname: Salter
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hawker
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman