@article{0888ad799a9c4740977336f43d84649a,
title = "Measuring treatment response to advance precision medicine for multiple sclerosis",
abstract = "Objective: To assess the independent contributions of clinical measures (relapses, Expanded Disability Status Scale [EDSS] scores, and neuroperformance measures) and nonclinical measures (new brain magnetic resonance imaging [MRI] activity and serum neurofilament light chain [sNfL] levels) for distinguishing natalizumab-treated from placebo-treated patients. Methods: We conducted post hoc analyses using data from the AFFIRM trial of natalizumab for multiple sclerosis. We used multivariable regression analyses with predictors (EDSS progression, no relapse, new or enlarging MRI activity, brain atrophy, sNfL levels, and neuroperformance worsening) to identify measures that independently discriminated between treatment groups. Results: The multivariable model that best distinguished natalizumab from placebo was no new or enlarging T2 or gadolinium-enhancing activity on MRI (odds ratio; 95% confidence interval: 7.2; 4.7–10.9), year 2 sNfL levels <97.5th percentile (4.1; 2.6–6.2), and no relapses in years 0–2 (2.1; 1.5–3.0). The next best-fitting model was a two-component model that included no MRI activity and sNfL levels <97.5th percentile at year 2. There was little difference between the three- and two-component models. Interpretation: Nonclinical measures (new MRI activity and sNfL levels) discriminate between treatment and placebo groups similarly to or better than clinical outcomes composites and have implications for patient monitoring.",
author = "Calabresi, {Peter A.} and Ludwig Kappos and Gavin Giovannoni and Tatiana Plavina and Irene Koulinska and Edwards, {Michael R.} and Bernd Kieseier and {de Moor}, Carl and Sotirchos, {Elias S.} and Elizabeth Fisher and Rudick, {Richard A.} and Alfred Sandrock",
note = "Funding Information: PAC: received consulting fees from Biogen, Disarm Therapeutics, and NervGen Pharma; grants from Annexon, Biogen, and Genentech. LK: University Hospital Basel received in the past 3 years and used exclusively for research support: steering committee/advisory board/consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df‐mp, Excemed, GeNeuro, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi, Sanofi‐Genzyme, Santhera, Teva, and Vianex; royalties for Neurostatus‐UHB Products and Services. GG: honoraria from AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex, FivePrime, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Sanofi‐Genzyme, Synthon, Teva Neuroscience, UCB Pharma, and Vertex Pharmaceuticals; compensation from Elsevier as co‐chief editor of ; research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis. TP, IK, BK, RAR, and MRE: Biogen employees at the time of the study, with stock/stock options in Biogen. ESS: advisory boards for Alexion, Genentech, and Viela Bio; speaker honoraria from Biogen and Viela Bio. CdM, EF, and AS: employees of and hold stock in Biogen. Multiple Sclerosis and Related Disorders Publisher Copyright: {\textcopyright} 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association",
year = "2021",
month = nov,
doi = "10.1002/acn3.51471",
language = "English (US)",
volume = "8",
pages = "2166--2173",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Inc.",
number = "11",
}