Prospective study validating a multidimensional treatment decision score predicting the 24-month outcome in untreated patients with clinically isolated syndrome and early relapsing–remitting multiple sclerosis, the ProVal-MS study
Authors: Bayas Antonios , Mansmann Ulrich , Ön Begum Irmak , Hoffmann Verena S. , Berthele Achim , Mühlau Mark , Kowarik Markus C. , Krumbholz Markus , Senel Makbule , Steuerwald Verena , Naumann Markus , Hartberger Julia , Kerschensteiner Martin , Oswald Eva , Ruschil Christoph , Ziemann Ulf , Tumani Hayrettin , Vardakas Ioannis , Albashiti Fady , Kramer Frank , Soto-Rey Iñaki , Spengler Helmut , Mayer Gerhard , Kestler Hans Armin , Kohlbacher Oliver , Hagedorn Marlien , Boeker Martin , Kuhn Klaus , Buchka Stefan , Kohlmayer Florian , Kirschke Jan S. , Behrens Lars , Zimmermann Hanna , Bender Benjamin , Sollmann Nico , Havla Joachim , Hemmer Bernhard ,   the ProVal-MS study group, Berlis Ansgar , Wiestler Benedikt , Kümpfel Tania , Seelos Klaus , Dünschede Jutta , Kemmner Roswitha , Beer Meinrad , Dietrich Jennifer , Schaller Jonas 
Published: March 2024

Abstract
Introduction
In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients.

Methods
ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing–Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing–Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed.

Perspective
Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage.
Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)—ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034