title: Design of TRUST, a non-interventional, multicenter, 3-year prospective study investigating an integrated patient management approach in patients with relapsing-remitting multiple sclerosis treated with natalizumab.
abstract: BACKGROUND
  Natalizumab provides rapid and high-efficacy control of multiple sclerosis disease activity with long-term stabilization. However, the benefits of the drug are countered by a risk of developing progressive multifocal leukoencephalopathy in patients infected with the John Cunningham Virus. Close monitoring is required in patients with increased progressive multifocal leukoencephalopathy risk receiving natalizumab in the long-term for an optimal benefit-risk evaluation. Standardized high-quality monitoring procedures may provide a superior basis for individual benefit and risk evaluation and thus improve treatment decisions. The non-interventional study TRUST was designed to capture natalizumab effectiveness under real-life conditions and to examine alternate approaches for clinical assessments, magnetic resonance imaging monitoring and use of biomarkers for progressive multifocal leukoencephalopathy risk stratification.
  
  
  METHODS
  TRUST is a non-interventional, multicenter, prospective cohort study conducted at approximately 200 German neurological centers. The study is intended to enroll 1260 relapsing-remitting multiple sclerosis patients with ongoing natalizumab therapy for at least 12 months. Patients will be followed for a period of 3 years, irrespective of treatment changes after study start. Data on clinical, subclinical and patient-centric outcomes will be documented in order to compare the effectiveness of continuous versus discontinued natalizumab treatment. Furthermore, the type and frequency of clinical, magnetic resonance imaging and biomarker assessments, reasons for continuation or discontinuation of therapy and the safety profile of natalizumab will be collected to explore the impact of a systematic patient management approach and its potential impact on patient outcome. Specifically, the role of biomarkers, the use of expert opinions, the impact of high-frequency magnetic resonance imaging assessment for early progressive multifocal leukoencephalopathy detection and the role of additional radiological and clinical expert advice will be explored.
  
  
  CONCLUSIONS
  TRUST was initiated in spring 2014 and enrollment is anticipated to be completed by mid 2016. Annual interim analyses will deliver continuous information and transparency with regard to the patient cohorts and the completeness and quality of data as well as closely monitor any safety signals in the natalizumab-treated cohort. The study's results may provide insights into opportunities to improve the benefit-risk assessment in clinical practice and support treatment decisions.
authors.affiliation: Department of Neurology, MS Center Dresden, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany. Tjalf.Ziemssen@uniklinikum-dresden.de.
authors.forename: Tjalf
authors.identifier: http://orcid.org/0000-0001-8799-8202
authors.initials: T
authors.lastname: Ziemssen
authors.affiliation: Department of Neurology, University Medicine Mannheim UMM, University of Heidelberg, Mannheim, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.affiliation: Medical Image Analysis Center (MIAC AG), Basel, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Wuerfel
authors.affiliation: Department of Neurology, Hospital Augsburg, Augsburg, Germany.
authors.forename: Antonios
authors.initials: A
authors.lastname: Bayas
authors.affiliation: Department of Neurology, Philipps University and University Clinics Gießen and Marburg, Marburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: Department of Neurology, Cologne General Hospitals, University of Cologne, Cologne, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen, Erlangen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Linker
authors.affiliation: Department of Neurology, Caritas Hospital Bad Mergentheim, Bad Mergentheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.affiliation: Department of Neurology, Jewish Hospital, Berlin, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Haas
authors.affiliation: Department of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
authors.affiliation: Biogen, Zug, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Meergans
authors.affiliation: Biogen, Ismaning, Germany.
authors.forename: Olof
authors.initials: O
authors.lastname: Harlin
authors.affiliation: Department of Neurology and Center for Neuropsychiatry, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D002985:Clinical Protocols; D019468:Disease Management; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: John Cunningham virus; Natalizumab; Progressive multifocal leukoencephalopathy; Relapsing-remitting multiple sclerosis