Explorative study of emerging blood biomarkers in progressive multiple sclerosis (EmBioProMS): Design of a prospective observational multicentre pilot study

Ahmed Abdelhak; Andre Huss; Alexander Stahmann; Makbule Senel; Markus Krumbholz; Markus C Kowarik; Joachim Havla; Tania Kümpfel; Ingo Kleiter; Isabella Wüstinger; Uwe K Zettl; Margit Schwartz; Romy Roesler; Tim Friede; Albert C Ludolph; Ulf Ziemann; Hayrettin Tumani

doi:10.1016/j.conctc.2020.100574

Explorative study of emerging blood biomarkers in progressive multiple sclerosis (EmBioProMS): Design of a prospective observational multicentre pilot study

Contemp Clin Trials Commun. 2020 May 19:18:100574. doi: 10.1016/j.conctc.2020.100574. eCollection 2020 Jun.

Authors

Ahmed Abdelhak^{1

2

3}, Andre Huss³, Alexander Stahmann⁴, Makbule Senel³, Markus Krumbholz^{1

2}, Markus C Kowarik^{1

2}, Joachim Havla⁵, Tania Kümpfel⁵, Ingo Kleiter^{6

7}, Isabella Wüstinger⁶, Uwe K Zettl⁸, Margit Schwartz⁸, Romy Roesler⁹, Tim Friede¹⁰, Albert C Ludolph³, Ulf Ziemann^{1

2}, Hayrettin Tumani^{3

9}

Affiliations

¹ Department of Neurology & Stroke, University Hospital of Tübingen, Tübingen, Germany.
² Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
³ Department of Neurology, University Hospital of Ulm, Ulm, Germany.
⁴ MS Forschungs- und Projektentwicklungs-gGmbH, MS-Registry by the German MS-Society, Hanover, Germany.
⁵ Institute of Clinical Neuroimmunology, Ludwig-Maximilians University, Munich, Germany.
⁶ Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Berg, Germany.
⁷ St. Josef-Hospital, Department of Neurology, Ruhr-University, Bochum, Germany.
⁸ Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany.
⁹ Fachklinik für Neurologie Dietenbronn, Schwendi, Germany.
¹⁰ Department of Medical Statistics, University Medical Centre Göttingen, Göttingen, Germany.

Abstract

Background: Defining clinical and subclinical progression in multiple sclerosis (MS) is challenging. Patient history, expanded disability status scale (EDSS), and magnetic resonance imaging (MRI) all have shortcomings and may underestimate disease dynamics. Emerging serum biomarkers such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) proved useful in many cross-sectional studies. However, longitudinal data on patients with progressive MS is scarce.

Objectives: To assess whether the serum biomarkers GFAP and NfL might differentiate between patients with progressive vs. non-progressive disease stages and predict the disease course according to the Lublin criteria.

Methods: EmBioProMS is a pilot, observational, prospective, multicentric study funded by the German Multiple Sclerosis Society (DMSG). 200 patients with MS according to the 2017 McDonald criteria and history of relapse-independent progression at any time (progressive MS, PMS), younger than 65 years, and with EDSS ≤ 6.5 will be recruited in 6 centres in Germany. At baseline, month 6, and 18, medical history, EDSS, Nine-Hole-Peg-Test (9-HPT), Timed-25-Foot-Walk-Test (T-25FW), Symbol-Digit-Modalities-Test (SDMT), serum GFAP, and NfL, MRI (at least baseline and month 18) and optional optical coherence tomography (OCT) will be performed. Disease progression before and during the study is defined by confirmed EDSS progression, increase by ≥ 20% in 9-HPT or T-25FW time.

Conclusions: This longitudinal multicentre study will reveal to what extent the prediction of disease progression in patients with PMS will be improved by the analysis of serum biomarkers in conjunction with routine clinical data and neuroimaging measures.