title: Study design of PANGAEA 2.0, a non-interventional study on RRMS patients to be switched to fingolimod.
abstract: BACKGROUND
  The therapeutic options for patients with Multiple Sclerosis (MS) have steadily increased due to the approval of new substances that now supplement traditional first-line agents, demanding a paradigm shift in the assessment of disease activity and treatment response in clinical routine. Here, we report the study design of PANGAEA 2.0 (Post-Authorization Non-interventional GermAn treatment benefit study of GilEnyA in MS patients), a non-interventional study in patients with relapsing-remitting MS (RRMS) identify patients with disease activity and monitor their disease course after treatment switch to fingolimod (Gilenya®), an oral medication approved for patients with highly active RRMS.
  
  
  METHODS
  In the first phase of the PANGAEA 2.0 study the disease activity status of patients receiving a disease-modifying therapy (DMT) is evaluated in order to identify patients at risk of disease progression. This evaluation is based on outcome parameters for both clinical disease activity and magnetic resonance imaging (MRI), and subclinical measures, describing disease activity from the physician's and the patient's perspective. In the second phase of the study, 1500 RRMS patients identified as being non-responders and switched to fingolimod (oral, 0.5 mg/daily) are followed-up for 3 years. Data on relapse activity, disability progression, MRI lesions, and brain volume loss will be assessed in accordance to 'no evidence of disease activity-4' (NEDA-4). The modified Rio score, currently validated for the evaluation of treatment response to interferons, will be used to evaluate the treatment response to fingolimod. The MS management software MSDS3D will guide physicians through the complex processes of diagnosis and treatment. A sub-study further analyzes the benefits of a standardized quantitative evaluation of routine MRI scans by a central reading facility. PANGAEA 2.0 is being conducted between June 2015 and December 2019 in 350 neurological practices and centers in Germany, including 100 centers participating in the sub-study.
  
  
  CONCLUSIONS
  PANGAEA 2.0 will not only evaluate the long-term benefit of a treatment change to fingolimod but also the applicability of new concepts of data acquisition, assessment of MS disease activity and evaluation of treatment response for the in clinical routine.
  
  
  BACKGROUND
  BfArM6532; Trial Registration Date: 20/05/2015.
authors: Zentrum für klinische Neurowissenschaften, Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Fetscherstr. 43, D-01307, Dresden, Germany. tjalf.ziemssen@uniklinikum-dresden.de.
authors: Tjalf
authors: http://orcid.org/0000-0001-8799-8202
authors: T
authors: Ziemssen
authors: Zentrum für klinische Neurowissenschaften, Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Fetscherstr. 43, D-01307, Dresden, Germany.
authors: Raimar
authors: R
authors: Kern
authors: Novartis Pharma GmbH, Roonstr. 25, D-90429, Nuernberg, Germany.
authors: Christian
authors: C
authors: Cornelissen
mesh_terms: D018450:Disease Progression; D004282:Documentation / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D057286:Electronic Health Records; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D011446:Prospective Studies; D012449:Safety; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Clinical routine; Efficacy; Fingolimod; Modified Rio score; Multiple sclerosis; NEDA; No evident disease activity; Relapsing remitting; Safety