Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;31(12):e16526.
doi: 10.1111/ene.16526. Epub 2024 Oct 24.

Treating to target in multiple sclerosis: Do we know how to measure whether we hit it?

Gabriel Bsteh  1   2 , Nik Krajnc  1   2 , Patrick Altmann  1   2 , Barry Hendin  3 , Trishna Bharadia  4 , Sonja Jaruszowic  5 , Fred Lublin  6 , Jiwon Oh  7 , Detlev Parow  8 , Annemie Ribbens  9 , Aoife Shields  10 , Dirk Smeets  9 , Eric Thouvenot  11   12 , Andrew Chan  13 , Thomas Berger  1   2
Affiliations

Treating to target in multiple sclerosis: Do we know how to measure whether we hit it?

Gabriel Bsteh et al. Eur J Neurol. 2024 Dec.

Abstract

Background and purpose: The rapidly evolving landscape of effective treatment options in multiple sclerosis has led to a shift of treatment objectives towards a treat-to-target approach aiming to suppress disease activity below the level of detectability early during the disease. To enable treat-to-target, a thorough reappraisal of available outcome measures with respect to their ability in this regard is required.

Methods: To that end, we conducted a comprehensive systematic literature review of more than 1000 studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 methodology focusing on underlying evidence as well as utility and implementability in clinical practice.

Results: From there, we propose a set of measurable outcomes for everyday routine clinical practice as well as advanced/aspirational measurables requiring additional resources. We also outline remaining knowledge/technology gaps that need to be overcome to enable a treat-to-target approach.

Conclusions: This work provides the basis for an evidence-based definition of outcome targets for relevant stakeholders and regulatory authorities.

Keywords: applicability; measures; multiple sclerosis; outcome; review; treat‐to‐target; utility.

PubMed Disclaimer

Conflict of interest statement

G.B. has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Celgene/BMS, Janssen, Lilly, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva and has received honoraria for consulting from Biogen, Celgene/BMS, Janssen, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis. N.K. has participated in meetings sponsored by or received speaker honoraria or travel funding from Alexion, BMS/Celgene, Janssen‐Cilag, Merck, Novartis, Roche, and Sanofi‐Genzyme and has held a grant for a Multiple Sclerosis Clinical Training Fellowship Program from the European Committee for Treatment and Research in Multiple Sclerosis. P.A. has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi‐Genzyme, and Teva and has received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Sanofi‐Genzyme, Roche, and Teva for a clinical study. B.H. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from Novartis, Genentech, Biogen, Sanofi, EMD Serono, Amgen, Bristol, Myers, Squibb, and Alexion. T.Bh. has received honoraria and consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Envision Pharma, Flatiron UK, Heel Pharma, Hollister, Insmed, King's College London, Medable, Medidata, Merck, MSD, Novartis, Oxford Health, Parexel, Pfizer, Queen Mary University London, Roche, Sandoz, Servier, Talking Medicines, Teva, UCB, University College London, and University of Nottingham. S.J. has participated in meetings sponsored by Merck, Roche, Sanofi‐Genzyme, and Teva and has received honoraria for consulting from Novartis. F.L. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from Biogen, EMD Serono, Novartis, Actelion/Janssen, Sanofi‐Genzyme, Roche/Genentech, Horizon Therapeutics/Amgen, Celgene/BMS, Mapi Pharma, Brainstorm Cell Therapeutics, Mylan/Viatris, Immunic, Avotres, Neurogene, LabCorp, Entelexo Biotherapeutics, Neuralight, SetPoint Medical, Hexal/Sandoz, Baim Institute, Sudo Biosciences, Lapix Therapeutics, Biohaven Pharmaceuticals, Abata Therapeutics, Cognito Therapeutics, and ImmPACT Bio. His institution has received financial support for research from Biogen, Novartis, Sanofi, NMSS, NIH, and Brainstorm Cell Therapeutics. J.O. has received grant funding from Biogen‐Idec, Roche, and EMD‐Serono and has received personal compensation for consulting or speaking from Biogen‐Idec, BMS, EMD‐Serono, Eli Lilly, Horizon Therapeutics, Novartis, Roche, and Sanofi‐Genzyme. D.P. has received honoraria for consulting and advising from Celgene/BMS, Janssen, and Novartis. A.R. has been an employee of icometrix (a company aiming to bring relevant outcome measures to clinical practice). A.S. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS including Biogen, Merck, Mylan, Novartis, Roche, Sanofi‐Genzyme, and Viatris. D.S. has been an employee of icometrix (a company aiming to bring relevant outcome measures to clinical practice). E.T. has received consulting and lecturing fees, travel grants, or unconditional research support from the following pharmaceutical companies: Actelion, Biogen, BMS, Merck, Novartis, Roche, and Teva Pharma. A.C. has received speaker/board honoraria from Actelion (Janssen/J&J), Alexion, Almirall, Bayer, Biogen, Celgene (BMS), Genzyme, Merck, Novartis, Roche, and Teva, all for hospital research funds. He has received research support from Biogen, CSL Behring, Genzyme, UCB, the European Union, and the Swiss National Foundation. T.Be. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS including Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, Genesis, GSK, GW/Jazz Pharma, Horizon, Janssen‐Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi‐Genzyme, Teva, and UCB. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Roche, Sanofi‐Genzyme, Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi‐Genzyme, and Teva.

Figures

FIGURE 1
FIGURE 1
Inclusion/exclusion process.
FIGURE 2
FIGURE 2
Clinical usefulness and quality of evidence for clinical outcomes in multiple sclerosis. Size of circles indicates available sample size of underlying evidence. 2MWT, 2 minute walking test; 6MWT, 6 minute walking test; 9HPT, 9‐Hole Peg Test; 10mWT, 10 minute walking test; BBS, Berg Balance SCale; BVMT‐R, Brief Visuospatial Memory Test Revised; CVLT‐II: California Verbal Learning Test II; EDSS, Expanded Disability Status Scale; HCVA, High Contrast Visual Acuity; LCVA, Low Contrast Visual Acuity; PASAT, Paced Auditory Serial Addition Test; SDMT, Symbol Digit Modalities Test; SPART, Spatial Recall Test; SRT, Selective Reminding Test; TMT, trail making test; TUG, Timed Up and Go Test; T25FW, Timed 25 Foot Walk Test; WLG, Word List Generation.
FIGURE 3
FIGURE 3
Clinical usefulness and quality of evidence for paraclinical outcomes in multiple sclerosis. Size of circles indicates available sample size of underlying evidence. CHI3L1, Chitinase 3 like 1; CSA, Cross Sectional Area; GCIPL, Ganglion Cell and Inner Plexiform Layer; GFAP, Glial Fibrillaric Astrocytic Protein; GM, Grey Matter; INL, Inner Nuclear Layer; NfH, Neurofilament Heavy chain; NfL, Neurofilament Light chain; ONL, Outer Nuclear Layer; pRNFL, peripapillary retinal nerve fiber layer; WM, White Matter; VEP, Visual Evoked Potentials.
FIGURE 4
FIGURE 4
Clinical usefulness and quality of evidence for patient‐reported outcomes in multiple sclerosis. Size of circles indicates available sample size of underlying evidence. ABC, Activities‐Specific Balance Confidence Scale; BDI, Beck Depression Inventory; CES‐D, Center for Epidemiological Studies Depression Scale; CIS‐20, Checklist Individual Strength; EQ‐5D, The EuroQol 5 Dimensions questionnaire; ESS, Epworth Sleepiness Scale; FAMS, Functional Assessment of Multiple Sclerosis; FIS, Fatigue Impact Scale; FSS, Fatigue Severity Scale; FSMC, Fatigue Scale of Motor and Cognitive Fatigue; GLTEQ, Godin Leisure‐Time Questionnaire; HADS, Hospital Anxiety and Depression Scale; HAQUAMS, Hamburg Quality of Life Questionnaire in Multiple Sclerosis; IPAQ, International Physical Activity Questionnaire; MFIS, Modified Fatigue Impact Scale; MSIS‐29, Multiple Sclerosis Impact Scale; MSQoL‐54, Multiple Sclerosis Quality of Life‐54; MSWS‐12, Multiple Sclerosis Walking Scale; MusiQoL, Multiple Sclerosis International Quality of Life; PDDS, Patient Determined Disease Steps; PHQ‐9, Patient Health Questionnaire; PSS, Perceived Stress Scale; PROMIS, Patient‐Reported Outcomes Measurement Information System; PSQI, Pittsburgh Sleep Quality Index; SF‐12, 12‐item Short Form Survey; SF‐36, 36‐item Short Form Survey; TSQM, Treatment Satisfaction Questionnaire for Medication; WPAI, Work Productivity and Activity Impairment.
FIGURE 5
FIGURE 5
Clinical usefulness and quality of evidence for combinations of outcomes in multiple sclerosis. Size of circles indicates available sample size of underlying evidence. BiCAMS, Brief International Cognitive Assessment for MS; BRB, Brief Repeatable Battery; MSFC, Multiple Sclerosis Functional Composite; MSPT, Multiple Sclerosis Performance Test; MRS, Modified Rio‐Score; NEDA‐2, No Evidence of Disease Activity 2; NEDA‐3, No Evidence of Disease Activity 3; NEDA‐4, No Evidence of Disease Activity 4; NEP‐2, No Evidence of Progression 2; NEP‐3, No Evidence of Progression 3; NEP‐4, No Evidence of Progression 4.
See this image and copyright information in PMC

References

    1. Compston A, Coles A. Multiple sclerosis. Lancet. 2002;359:1221‐1231. - PubMed
    1. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease‐modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3‐18. - PubMed
    1. Yeung J, Bourcier M, Gooderham MJ, et al. Management of moderate‐to‐severe plaque psoriasis with biologics: a treat‐to‐target position paper. Dermatol Ther. 2022;35:e15777. - PubMed
    1. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis. Neurology. 1996;46:907‐911. - PubMed
    1. Bielekova B, Kadom N, Fisher E, et al. MRI as a marker for disease heterogeneity in multiple sclerosis. Neurology. 2005;65:1071‐1076. - PubMed

Publication types

MeSH terms