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

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.

Conflict of interest statement

AA received research funding from DMSG and travel grants from 10.13039/100005614Biogen, AS has received institutional research grants from 10.13039/100004334Merck and 10.13039/100004336Novartis, all outside the submitted work. MS received consulting and/or speaker honoraria as well as travel reimbursements from Bayer, Biogen, Celgene, Roche, Sanofi Genzyme and TEVA and research funding from the Hertha-Nathorff-Program and the 10.13039/501100008977University of Ulm. MK received financial support from 10.13039/100005614Biogen, 10.13039/100006436Celgene, 10.13039/100004334Merck, 10.13039/100004336Novartis, 10.13039/100004337Roche, and Sanofi-Genzyme. MCK receives financial support from Merck, Novartis, Biogen, Celgene and Roche. JH reports personal fees and non-financial support from Merck, Novartis, Roche, Santhera, Biogen, Alexion, Sanofi Genzyme, and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. JH is (partially) funded by the German Federal Ministry of Education and Research (Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H] (DIFUTURE)). TK has received speaker honoraria including advisory boards from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche Pharma and Biogen as well as grant support from Novartis and Chugai Pharma in the past. IK has received speaker honoraria and travel funding from Bayer, Biogen, Novartis, Merck, Sanofi Genzyme, Roche; speaker honoraria from Mylan; travel funding from the Guthy-Jackson Charitable Foundation; consulted for Alexion, Bayer, Biogen, Celgene, Chugai, IQVIA, Novartis, Merck, Roche; received research support from Chugai, Diamed; all outside the submitted work. UKZ received travel compensation for research meetings from Aventis, Bayer, Biogen, Celgene as well as speakers fee from Almirall, Alexion, Bayer, Biogen, Merck, Novartis, Roche and Teva. TF reports personal fees for consultancies (including data monitoring committees) in the past three years from Bayer, BiosenseWebster, Boehringer Ingelheim, Cardialysis, CSL Behring, Sankyo, Enanta, Feldmann Patent Attorneys, Fresenius Kabi, Galapagos, IQVIA, Janssen, Mediconomics, Novartis, Penumbra, Roche, SGS, and Vifor; all outside the submitted work. ACL received personal fees from Hoffmann-La Roche, Novartis, Desitin Pharma, Syneos Health, Teva Pharmaceutical Industries, Boehringer Ingelheim, Biogen, and Mitsubishi Pharma for consultancy services. UZ received financial support from Biogen Idec GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH, Pfizer, CorTec GmbH, Medtronic GmbH, and research support from European Research Council, DFG, BMBF, Servier, and Janssen Pharmaceuticals. HT reports personal fees and/or research grants from Fresenius Medical Care GmbH and Fresenius Medical Care Deutschland GmbH, Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, DMSG, and BMBF. All other authors declare no competing interests.

© 2020 The Authors.

Figures

Fig. 1

Study flowchart. + only 25% of the patients are allowed to have EDSS scores above 5.5.

Fig. 2

Electronic data capture structure applied in the EmBioProMS study.