BACKGROUND: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application. OBJECTIVE: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs). METHODS: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios. sNfL levels were defined as "high" (>90th percentile) vs "normal" (<80th percentile), based on normative values of control persons. In three rounds, 10 international and 18 Swiss MS experts, and 3 patient consultants rated their agreement on treatment algorithms. Consensus thresholds were defined as moderate (50%-79%), broad (80%-94%), strong (≥95%), and full (100%). RESULTS: The Delphi provided 9 escalation algorithms (e.g. initiating treatment based on high sNfL), 11 horizontal switch (e.g. switching natalizumab to another high-efficacy DMT based on high sNfL), and 3 de-escalation (e.g. stopping DMT or extending intervals in B-cell depleting therapies). CONCLUSION: The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice.

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Center of Clinical Neuroscience Neurological Clinic University Hospital Carl Gustav Carus TU Dresden Dresden Germany

Department of Clinical Research University Hospital Basel University of Basel Basel Switzerland

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology Bern University Hospital University of Bern Bern Switzerland

Department of Neurology Cantonal Hospital Aarau Aarau Switzerland

Department of Neurology Institute of Translational Neurology University Hospital Münster Münster Germany

Department of Neurology Karolinska University Hospital Stockholm Sweden

Department of Neurology Klinikum rechts der Isar Technical University of Munich Munich Germany

Department of Neurology Medical University of Graz Graz Austria

Department of Neurology Ruhr University Bochum St Josef Hospital Bochum Germany

Department of Neurology University Hospital Basel University of Basel Basel Switzerland

Department of Neurology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Neurology University Hospital Zurich Zurich Switzerland

Department of Neurology University of Regensburg Regensburg Germany

Department of Neurology University Teaching and Research Hospital St Gallen St Gallen Switzerland

Departments of Biomedicine and Clinical Research University Hospital Basel University of Basel Basel Switzerland

Division of Neurology Department of Clinical Neurosciences Faculty of Medicine Geneva University Hospitals Geneva Switzerland

Division of Neurology Department of Internal Medicine Bürgerspital Solothurn Solothurn Switzerland

Faculty of Biomedical Sciences Università della Svizzera Italiana Lugano Switzerland

Institute of Pharmacology and Toxicology University of Zurich Zurich Switzerland

Multiple Sclerosis Center Neurocenter of Southern Switzerland Ospedale Regionale di Lugano Lugano Switzerland

Multiple Sclerosis Centre of Catalonia Vall d'Hebron Barcelona Hospital Barcelona Spain

Multiple Sclerosis Centre University Hospital Basel Basel Switzerland

Neuroimmunology Unit Center for Molecular Medicine Karolinska Institute Stockholm Sweden

Neurologic Clinic and Policlinic MS Centre University Hospital Basel Basel Switzerland

Neurozentrum Oberaargau Langenthal Switzerland

Patient Consultant Basel Switzerland

Research Center for Clinical Neuroimmunology and Neuroscience Basel University Hospital Basel University of Basel Basel Switzerland

Service of Neurology Department of Clinical Neurosciences Lausanne University Hospital University of Lausanne Lausanne Switzerland

Translational Biomarker Research Group Department of Medicine Faculty of Medicine University of Geneva Geneva Switzerland

Translational Imaging in Neurology Basel Department of Medicine and Biomedical Engineering University Hospital Basel University of Basel Basel Switzerland

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