title: Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.
abstract: BACKGROUND
  Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Brain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 15 healthy controls. Percentages of whole brain and tissue-specific volume change were measured from baseline (0 months) to 3 months, from 3 to 6 months, and from baseline to 6 months using SIENAX Multi Time Point (SX-MTP) algorithms. Immunological status of patients was also determined and correlations between subsets of T cells and changes in brain volume were assessed.
  
  
  RESULTS
  Interferon β-1a 44 μg SC tiw in 23 patients with RRMS resulted in significant reductions in whole brain and gray matter tissue volume early in the treatment course (baseline to 3 months; mean change; -0.95%; P = 0.030, -1.52%; P = 0.004, respectively), suggesting a short-term treatment-induced pseudoatrophy effect. From baseline to 6 months, there were significant correlations observed between decreased T- cell expression of IL-17 F and decreased whole brain and brain tissue-specific volume.
  
  
  CONCLUSIONS
  These findings are consistent with the interpretation of the pseudoatrophy effect as resolution of inflammation following treatment initiation with interferon β-1a 44 μg SC tiw, rather than disease-related tissue loss.
  
  
  BACKGROUND
  ClinicalTrials.gov; NCT01085318.
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. mgdwyer@bnac.net.|Department of Biomedical Informatics, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. mgdwyer@bnac.net.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dwyer
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. rzivadinov@bnac.net.|Department of Neurology, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. rzivadinov@bnac.net.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Department of Neurology, Microbiology and Immunology, University of North Carolina at Chapel Hill, 125 Mason Farm Rd., 6109D Neuroscience Research Bldg, CB #7125, Chapel Hill, NC, 27599, USA. yztao@med.unc.edu.
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurology, Microbiology and Immunology, University of North Carolina at Chapel Hill, 125 Mason Farm Rd., 6109D Neuroscience Research Bldg, CB #7125, Chapel Hill, NC, 27599, USA. zhangx@neurology.unc.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. ckennedy@bnac.net.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. npbergsland@bnac.net.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. dramasamy@bnac.net.
authors.forename: Deepa P
authors.initials: DP
authors.lastname: Ramasamy
authors.affiliation: Department of Neurology, Buffalo Neuroimaging Analysis Center, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. jdurfee@bnac.net.
authors.forename: Jackie
authors.initials: J
authors.lastname: Durfee
authors.affiliation: Department of Neurology, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. hojnacki@buffalo.edu.
authors.forename: David
authors.initials: D
authors.lastname: Hojnacki
authors.affiliation: Department of Neurology, State University of New York at Buffalo, 100 High St, Buffalo, NY, 14203, USA. bweinstock-guttman@kaleidahealth.org.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: EMD Serono, Inc., One Technology Pl, Rockland, MA, 02370, USA. brooke.hayward@emdserono.com.
authors.forename: Brooke
authors.initials: B
authors.lastname: Hayward
authors.affiliation: EMD Serono, Inc., One Technology Pl, Rockland, MA, 02370, USA. fernando.dangond@emdserono.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dangond
authors.affiliation: Department of Neurology, Microbiology and Immunology, University of North Carolina at Chapel Hill, 125 Mason Farm Rd., 6109D Neuroscience Research Bldg, CB #7125, Chapel Hill, NC, 27599, USA. markovics@neurology.unc.edu.
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D016899:Interferon-beta / Q000008:administration & dosage*; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: C440021:IL17F protein, human; D020381:Interleukin-17; D016899:Interferon-beta; D000068556:Interferon beta-1a