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. 2020 Nov;26(13):1658-1669.
doi: 10.1177/1352458519877810. Epub 2019 Oct 15.

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS

Mar Tintore  1 , Georgina Arrambide  1 , Susana Otero-Romero  2 , Pere Carbonell-Mirabent  1 , Jordi Río  1 , Carmen Tur  3 , Manuel Comabella  1 , Carlos Nos  1 , María Jesús Arévalo  1 , Elisenda Anglada  1 , Rebeca Menendez  1 , Luciana Midaglia  1 , Ingrid Galán  1 , Angela Vidal-Jordana  1 , Joaquin Castilló  1 , Patricia Mulero  1 , Ana Zabalza  1 , Breogan Rodríguez-Acevedo  1 , Marta Rodriguez  1 , Carmen Espejo  1 , Joao Sequeira  1 , Raquel Mitjana  4 , Andrea de Barros  4 , Deborah Pareto  4 , Cristina Auger  4 , Santiago Pérez-Hoyos  5 , Jaume Sastre-Garriga  1 , Alex Rovira  4 , Xavier Montalban  6
Affiliations

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS

Mar Tintore et al. Mult Scler. 2020 Nov.

Abstract

Objective: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort.

Methods: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years).

Results: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL.

Conclusion: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.

Keywords: Clinically isolated syndromes; MRI; disease-modifying treatment; multiple sclerosis; prediction; prognosis.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.T. has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis and Teva Pharmaceuticals. M.T. is co-editor of Multiple Sclerosis Journal – Experimental, Translational and Clinical. G.A. has received compensation for consulting services or participation in advisory boards from Biogen-Idec, Sanofi and Merck; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche and Stendhal; and speaking honoraria from Sanofi and Merck. S.O.-R. has received compensation for consulting services from Biogen-Idec and Genzyme, and research support from Novartis. P.C. has received travel expenses from Biogen. P.C.’s yearly salary is supported by a grant from Biogen to Fundacio privada Cemcat towards statistical analysis. J.R. has received speaking honoraria and personal compensation for participating on Advisory Boards from Almirall, Bayer Schering Healthcare, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Teva and Sanofi-Aventis. C.T. has received a post-doctoral research ECTRIMS fellowship (2015). C.T. has received honoraria and support for travelling from Novartis, Teva Pharmaceuticals, Ismar Healthcare and F. Hoffmann-La Roche, Ltd. M.C. has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis and Novartis. C.N. has received funding for travel from Biogen-Idec and F. Hoffmann-La Roche, Ltd., and speaker honoraria from Novartis. A.V.-J. receives support for contracts Juan Rodes (JR16/00024) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain, and has received speaking honoraria and travel expenses from Novartis, Roche, Teva, Biogen and Genzyme-Sanofi. D.P. has received speaking honoraria from Novartis and Biogen. C.A. has received speaking honoraria from Novartis, Biogen and Stendhal. J.S.-G. has received compensation for participating on Advisory Boards, speaking honoraria and travel expenses for scientific meetings, consulting services or research support from Celgene, Novartis, Biogen, Teva, Merck, Almirall and Genzyme. A.R. serves on scientific advisory boards for Biogen-Idec, Novartis, Genzyme, Bayer and OLEA Medical, and on the editorial board of the American Journal of Neuroradiology; he has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Novartis and Biogen-Idec and has research agreements with Siemens AG. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past with Actelion, Almirall, Bayer, Biogen, Celgene, Genzyme, Hoffmann-La Roche, Novartis, Oryzon Genomics, Sanofi-Genzyme and Teva Pharmaceutical. M.J.A., L.M., I.G., C.E., J.C., PM., B.R.-A., S.P.-H., R.M., M.R., E.A., R.M., A.Z. and A.d.B. report no disclosures.

Figures

Figure 1.
Figure 1.
Flowchart: patient’s disposition. CIS: clinically isolated syndrome.
Figure 2.
Figure 2.
Heat maps showing the proportion of patients reaching McDonald MS, CDMS, and EDSS of 3.0 and 6.0 according to the number of baseline T2 lesions.
Figure 3.
Figure 3.
Multivariable Cox model results for reaching an EDSS of 3.0 in treated patients: initiation of DMT before or after CDMS. EDSS: Expanded Disability Status Scale; DMT: disease-modifying treatment; CDMS: clinically definite multiple sclerosis; OB: oligoclonal bands; HR: hazard ratio; CI: confidence interval.
Figure 4.
Figure 4.
Baseline MRI characteristics and cut-offs obtained at baseline for aggressive and non-aggressive MS. IQR: interquartile range; SD: standard deviation; EDSS: Expanded Disability Status Scale, sens: sensibility, spec: specificity, acc: accuracy, PPV: positive predictive value, NPV: negative predictive value; LR+: positive likelihood ratio.
See this image and copyright information in PMC

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