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2. Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared With Healthy Ethnicity-Matched Controls

Author

Van den Hof, Malon, Haneveld, Mirthe J Klein, Blokhuis, Charlotte, Scherpbier, Henriette J, Jansen, Hans PG, Kootstra, Neeltje A, Dallinga-Thie, Geesje M, Van Deventer, Sander JH, Tsimikas, Sotirios, Pajkrt, Dasja, Van den Hof, M, Blokhuis, C, Cohen, S, Pajkrt, D, Scherpbier, HJ, Kuijpers, TW, van der Plas, A, Weijsenfeld, A, Stege, JS ter, Kootstra, NA, Caan, MWA, Mutsaerts, HJMM, Majoie, CBLM, Demirkaya, N, Verbraak, FD, Schmand, B, Geurtsen, G, Mathot, RAA, Wit, FWNM, Reiss, P, Teunissen, CE, Kuhle, J, and Meijer, JCM

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Pediatric, Clinical Research, Atherosclerosis, Prevention, Infectious Diseases, Heart Disease, Good Health and Well Being, cardiovascular disease risk, lipids, lipoprotein(a), MRI, perinatal HIV infection, NOVICE study group, Clinical sciences, Medical microbiology
Abstract

BackgroundHIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)-treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+.MethodsWe cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8-18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease- and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models.ResultsPHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6-82.4] vs 21.8 [16.8-46.6] mg/dL; P = .033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV- or cART-related variables or with neuroimaging outcomes.ConclusionscART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub)clinical CVD measurements in cART-treated PHIV+ patients.Dutch trial register numberNRT4074.

Published
2019

4. Multiple sclerosis registries in Europe – An updated mapping survey

Author

Glaser, A., Stahmann, A., Meissner, T., Flachenecker, P., Horáková, D., Zaratin, P., Brichetto, G., Pugliatti, M., Rienhoff, O., Vukusic, S., de Giacomoni, A.C., Battaglia, M.A., Brola, W., Butzkueven, H., Casey, R., Drulovic, J., Eichstädt, K., Hellwig, K., Iaffaldano, P., Ioannidou, E., Kuhle, J., Lycke, K., Magyari, M., Malbaša, T., Middleton, R., Myhr, K.M., Notas, K., Orologas, A., Otero-Romero, S., Pekmezovic, T., Sastre-Garriga, J., Seeldrayers, P., Soilu-Hänninen, M., Stawiarz, L., Trojano, M., Ziemssen, T., Hillert, J., and Thalheim, C.

Published
2019
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5. Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis

Author

Cagol, A., Fuertes, N.C., Stoessel, M., Barakovic, M., Schaedelin, S., D'Souza, M., Würfel, J., Brandt, A.U., Kappos, L., Sprenger, T., Naegelin, Y., Kuhle, J., Granziera, C., and Papadopoulou, A.

Subjects
Function and Dysfunction of the Nervous System
Abstract

BACKGROUND: Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). OBJECTIVE: To investigate associations among OCT changes, MRI measurements of global and regional brain volume loss, and physical and cognitive impairment in PwMS. METHODS: 95 PwMS and 52 healthy controls underwent OCT and MRI examinations. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell/inner plexiform layer (GCIPL) volume were measured. In PwMS disability was quantified with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Associations between OCT, MRI, and clinical measures were investigated with multivariable regression models. RESULTS: In PwMS, pRNFL and GCIPL were associated with the volume of whole brain (p

Published
2023

6. Foetal Allogeneic Intracerebroventricular Neural Stem Cell Transplantation in People with Secondary Progressive Multiple Sclerosis: A phase I dose-escalation clinical trial

Author

Leone, MA, primary, Gelati, M, additional, Profico, DC, additional, Conti, C, additional, Spera, C, additional, Muzi, G, additional, Grespi, V, additional, Bicchi, I, additional, Ricciolini, C, additional, Ferrari, D, additional, Zarrelli, M, additional, Amoruso, L, additional, Placentino, G, additional, Crociani, P, additional, Apollo, F, additional, Di Viesti, P, additional, Fogli, D, additional, Popolizio, T, additional, Colosimo, C, additional, Frondizi, D, additional, Stipa, G, additional, Tinella, E, additional, Ciampini, A, additional, Sabatini, S, additional, Paci, F, additional, Silveri, G, additional, Gobbi, C, additional, Pravatà, E, additional, Zecca, E, additional, Balzano, RF, additional, Kuhle, J, additional, Copetti, M, additional, Fontana, A, additional, Carella, M, additional, D’Aloisio, G, additional, Abate, L, additional, Ventura Carmenate, Y, additional, Pluchino, S, additional, Peruzzotti-Jametti, L, additional, and Vescovi, AL, additional

Published
2022
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8. Comparative effectiveness of autologous haematopoietic stem cell transplantation vs. fingolimod, ocrelizumab and natalizumab in relapsing-remitting MS

Author

Atkins, H., Burman, J., Massey, J., Sutton, I., Withers, B., Macdonell, R., Grigg, A., Torkildsen, O., Bo, L., Lehmann, A., Horakova, D., Havrdova, E., Krasulova, E., Trneny, M., Kozak, T., van der Walt, A., Butzkueven, H., McCombe, P., Van Wijmeersch, B., Buzzard, K., Skibina, O., Lechner-Scott, J., Willekens, B., Barnett, M., Cartechini, E., Ozakbas, S., Alroughani, R., Izquierdo, G., Boz, C., Kalincik, T., Sharman, S., Roos, I., Freedman, M., Eichau, S., Snowden, J., Sharrack, B., Turkoglu, R., Prevost, J., Slee, M., Soysal, A., Khoury, S., Lugaresi, A., Onofrj, M., Grammond, P., Duquette, P., Girard, M., Prat, A., Terzi, M., Patti, F., and Kuhle, J.

Published
2022

9. Emulating randomized clinical trials in relapsing-remitting multiple sclerosis with nonrandomized real-world evidence: an application using data from the MSBase registry

Author

Karabudak, R., Boz, C., Khoury, S., Girard, M., Turkoglu, R., Soysal, A., Alroughani, R., Terzi, M., Horakova, D., Havrdova, E., Ozakbas, S., Ponzano, M., Grammond, P., Yamout, B., Kalincik, T., Prat, A., Eichau, S., Izquierdo, G., Kuhle, J., Patti, F., Lechner-Schott, J., Sormani, M. P., Butzkueven, H., van der Walt, A., and Signori, A.

Published
2022

10. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Coles, A., Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Alroughani, R., Patti, F., Onofrj, M., Eichau, S., Girard, M., Grand'Maison, F., Yamout, B., Sajedi, S. A., Amato, M. P., Altintas, A., Skibina, O., Grammond, P., Butzkueven, H., Maimone, D., Lechner-Scott, J., Soysal, A., John, N., Gerlach, O., Iuliano, G., Foschi, M., Van Pesch, V., Cartechini, E., Kuhle, J., Sa, M. J., Kermode, A., Gouider, R., Hodgkinson, S., McCombe, P., Sanchez-Menoyo, J. L., Singhal, B., Blanco, Y., Hughes, S., McGuigan, C., Taylor, B., Habek, M., Al-Asmi, A., Mihaela, S., Castillo Trivino, T., Al-Harbi, T., Rojas, J. I., Gray, O., Khurana, D., Van Wijmeersch, B., Kalincik, T., and Brown, J. W. L.

Published
2022

11. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Butler, E., Van Pesch, V., Shalaby, N., Kermode, A., Maimone, D., Blanco, Y., Altintas, A., Turkoglu, R., Butzkueven, H., Van der Walt, A., Skibina, O., Buzzard, K., Lechner-Scott, J., Grammond, P., Khoury, S. J., Yamout, B., Grand'Maison, F., Karabudak, R., Amato, M. P., Terzi, M., Duquette, P., Girard, M., Prat, A., Weinstock-Guttman, B., Lugaresi, A., Onofrj, M., Zakaria, M., Boz, C., Eichau, S., Izquierdo, G., Shaygannejad, V., Alroughani, R., Patti, F., Havrdova, E. K., Horakova, D., Ozakbas, S., Sanchez, M. Martinez, Malpas, C., Simpson-Yap, S., Roos, I., Sharmin, S., Sidhom, Y., Gouider, R., Gerlach, O., Soysal, A., Barnett, M., Kuhle, J., Hughes, S., Sa, M. Jose, and Kalincik, T.

Published
2022

12. Efficacy and persistence between dimethyl fumarate, fingolimod, and ocrelizumab after natalizumab cessation

Author

Macdonell, R., Zhu, C., Kalincik, T., Horakova, D., Zhen, Z., Buzzard, K., Skibina, O., Alroughani, R., Izquierdo, G., Eichau, S., Kuhle, J., Patti, F., Grand'Maison, F., Hodgkinson, S., Grammond, P., Lechner-Scott, J., Butler, E., Prat, A., Girard, M., Butzkueven, H., Van der Walt, A., Merlo, D., Monif, M., Jokubaitis, V., Khoury, S. J., Yamout, B., Garber, J., Kermode, A., Van Hijfte, L., Laureys, G., Boz, C., Terzi, M., Prevost, J., Gerlach, O., Van Wijmeersch, B., Barnett, M., Van Pesch, V., Sa, M. Jose, Slee, M., Ozakbas, S., Weinstock-Guttman, B., and Duquette, P.

Published
2022

13. A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis

Author

Skibina, O., Msbase and Danish Sclerosis Registry Study Grp, Msbase and Danish Sclerosis Registry Study Grp, Kalincik, T., Magyari, M., Gray, O., Sellebjerg, F., Soysal, A., Grand'Maison, F., Grammond, P., John, N., Van Hijfte, L., Laureys, G., Terzi, M., Kuhle, J., Lechner-Scott, J., Butzkueven, H., Van der Walt, A., Buzzard, K., Ozakbas, S., Alroughani, R., Boz, C., MacDonnell, G., Hughes, S., and Roos, I.

Published
2022

15. Real-World Comparative Effectiveness and Persistence of Cladribine Tablets and Other Oral Disease-Modifying Treatments for Multiple Sclerosis from GLIMPSE: Results from the MSBase Registry

Author

Spitaleri, D., Kuhle, J., Ozakbas, SERKAN, Patti, F., Ampapa, R., Horakova, D., Soysal, A., Butzkueven, H., Spelman, T., Lechner-Scott, J., Yamout, B., Alroughani, R., Terzi, M., Hodgkinson, S., Sanchez-Menoyo, J., Blanco, Y., Van Pesch, V., Van der Walt, A., Kalincik, T., Laureys, G., Wong, S., Tundia, N., Altintas, A., Oh, J., Gerlach, O., Al-Asmi, A., and Macdonell, R.

Published
2022

18. Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression (vol 208, 106180, 2021)

Author

De Brouwer, E, Becker, T, Moreau, Y, Havrdova, EK, Trojano, M, Eichau, S, Ozakbas, S, Onofrj, M, Grammond, P, Kuhle, J, Kappos, L, Sola, P, Cartechini, E, Lechner-Scott, J, Alroughani, R, Gerlach, O, Kalincik, T, Granella, F, Grand'Maison, F, Bergamaschi, R, Sa, MJ, Van Wijmeersch, B, Soysal, A, Sanchez-Menoyo, JL, Solaro, C, Boz, C, Iuliano, G, Buzzard, K, Aguera-Morales, E, Terzi, M, Trivio, TC, Spitaleri, D, Van Pesch, V, Shaygannejad, V, Moore, F, Oreja-Guevara, C, Maimone, D, Gouider, R, Csepany, T, Ramo-Tello, C, and Peeters, L

Published
2022

21. Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials

Author

Hardmeier, M., Schlaeger, R., Lascano, A. M., Toffolet, L., Schindler, C., Gobbi, C., Lalive, P., Kuhle, J., Kappos, L., and Fuhr, P.

Subjects
Disability Evaluation, Multiple Sclerosis, Neurology, Physiology (medical), Disease Progression, Humans, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Prognosis, Evoked Potentials, Sensory Systems, Biomarkers
Abstract

OBJECTIVE: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. METHODS: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. RESULTS: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R(2)adj: 0.24), while EDSS and age did not. Tibial qSEP (R(2)adj: 0.22) and qMEP (R(2)adj: 0.26) were the best single modality predictors, outperformed by their combination (R(2)adj: 0.32). CONCLUSIONS: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. SIGNIFICANCE: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS.

Published
2021

22. Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis

Author

Maggi P, Kuhle J, Schädelin S, van der Meer F, Weigel M, Galbusera R, Mathias A, Lu PJ, Rahmanzadeh R, Benkert P, La Rosa F, Bach Cuadra M., Bach Cuadra M, Sati P, Théaudin M, Pot C, van Pesch V, Leppert D, Stadelmann C, Kappos L, Du Pasquier R, Reich DS, Absinta M, and Granziera C

Abstract

Objective:To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. Methods:In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. Results:In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68;p< 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4;p= 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (βadd, 16.3; 95% confidence interval [CI], 4.6-28.0;p< 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; βadd, 30.4; 95% CI, 15.6-45.2;p< 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (βadd, 1.1; 95% CI, 0.3-1.9;p< 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center:p= 0.004 andp= 0.0002, respectively). Conclusion:Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Published
2021

24. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, Albert, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, Charlotte E, Universitat Autònoma de Barcelona, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Basic (bio-) Medical Sciences, Ayşe, Altıntaş, Leurs, C.E., Twaalfhoven, H.A.M., Lissenberg-Witte, B.I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L.M., Alvarez-Cermeño, J.C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L.M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Rejdak, K., Frederiksen, J.L., Pihl-Jensen, G., Jensen, P.E.H., Khalil, M., Voortman, M.M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B.M.J., Killestein, J., Bridel, C., Teunissen, C., School of Medicine, Department of Neurology, Neurology, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Department of Anatomy and Neurosciences [Amsterdam, The Netherlands] (Amsterdam Neuroscience), Section Clinical Neuroanatomy [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam]-VU University Medical Center [Amsterdam], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Cliniques Universitaires Saint-Luc [Bruxelles], Clinical Centre of Serbia, Università degli Studi di Ferrara (UniFE), University Hospital Basel [Basel], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Red Española de Esclerosis Múltiple (REEM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Neurology, Medical University of Innsbruck, Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d'Hebron University Hospital [Barcelona], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Szeged [Szeged], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Koç University, Medical University of Lublin, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Department of Neurology, AZ Sint Jan Brugge Oostende, Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Amsterdam Neuroscience [Pays-Bas], and Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam]

Subjects
KFLC (kappa free light chain), Adult, Male, Multiple Sclerosis, Clinical Neurology, Esclerosi múltiple, CSF, CSF (cerebrospinal fluid), Immunoglobulin light chain, Sensitivity and Specificity, NO, Multiple sclerosis, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Immunoglobulin lambda-Chains, Humans, Medicine, Diagnostic biomarker, biomarkers, KFLC, OCB, 030304 developmental biology, 0303 health sciences, business.industry, Biochemical markers, Oligoclonal Bands, Reproducibility of Results, Middle Aged, OCB (oligoclonal IgG band), Free Light Chain, Biomarkers, Neurology, Multicenter study, Marcadors bioquímics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Original Research Papers, 030217 neurology & neurosurgery, Kappa
Abstract

Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA

Published
2020

25. Serum neurofilament light and tau as markers for overall mortality in the elderly general population – an analysis from the MEMO cohort study

Author

Rübsamen, N, Maceski, A, Leppert, D, Kuhle, J, Peters, A, Karch, A, and Berger, K

Subjects
SIMOA, ddc: 610, nervous system, biomarker, prognosis, tau, neurofilament, 610 Medical sciences, Medicine, mortality
Abstract

Background: Neurofilament light (NfL) is assumed to be released from dying neurons. Detection of NfL in serum is a quantitative measure of neuro-axonal injury. Tau, a microtubule-associated protein in neurons, is complementary to NfL because of its strong association with the process of overall brain[for full text, please go to the a.m. URL], 65th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), Meeting of the Central European Network (CEN: German Region, Austro-Swiss Region and Polish Region) of the International Biometric Society (IBS)

Published
2021
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26. Cortical lesion detection using FLAWS in multiple sclerosis

Author

Muller, J., Rahmanzadeh, R., Tsagkas, C., Barakovic, M., Lu, P. -J., Yaldizli, O., Weigel, M., Beaumont, J., La Rosa, F., Cuadra, M. Bach, Kappos, L., Kuhle, J., Gambarota, G., Granziera, C., Jonchère, Laurent, University Hospital Basel [Basel], Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne (UNIL), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lausanne = University of Lausanne (UNIL)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Meeting Abstract

Published
2021

27. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

Author

Schindler, P., Grittner, U., Oechtering, J., Leppert, D., Siebert, N., Duchow, A.S., Oertel, F.C., Asseyer, S., Kuchling, J., Zimmermann, H.G., Brandt, A.U., Benkert, P., Reindl, M., Jarius, S., Paul, F., Bellmann-Strobl, J., Kuhle, J., and Ruprecht, K.

Subjects
Adult, Male, Serum, Research, Neuromyelitis Optica, Aquaporin-4 immunoglobulin G, Biomarker, Middle Aged, Prognosis, Glial fibrillary acidic protein, Severity of Illness Index, Neurofilament light chain protein, Neuromyelitis optica spectrum disorder, Neurofilament Proteins, Humans, Female, Myelin oligodendrocyte glycoprotein immunoglobulin G, Neurology. Diseases of the nervous system, Function and Dysfunction of the Nervous System, RC346-429, Biomarkers, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Aged, Autoantibodies
Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG(+)) NMOSD. Methods: sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG(+) patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG(+)) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG(+) patients over a median observation period of 4.25 years. Results: In patients with AQP4-IgG(+) NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG(+) patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG(+), but not MOG-IgG(+) patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = - 1.28, p = 0.01). While in AQP4-IgG(+), but not MOG-IgG(+) patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = - 1.75, p = 0.06) in patients with AQP4-IgG(+) NMOSD. Patients with AQP4-IgG(+) NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP

Published
2021

28. Neurofilament light chain as a marker for cortical atrophy in multiple sclerosis without radiological signs of disease activity

Author

Ineichen, B. V., primary, Moridi, T., additional, Ewing, E., additional, Ouellette, R., additional, Manouchehrinia, A., additional, Stawiarz, L., additional, Ferreira, D., additional, Muehlboeck, S. J., additional, Kuhle, J., additional, Westman, E., additional, Leppert, D., additional, Hillert, J., additional, Olsson, T., additional, Kockum, I., additional, Piehl, F., additional, and Granberg, T., additional

Published
2021
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31. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author

Disanto, G1, Adiutori, R2, Dobson, R2, Martinelli, V3, Dalla Costa G3, Runia, T4, Evdoshenko, E5, Thouvenot, E6, Trojano, M7, Norgren, N8, Teunissen, C9, Kappos, L10, Giovannoni, G2, Kuhle, J, Bianchi, L, Topping, J, Bestwick, Jp, Meier, Uc, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, Jc, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, Ad, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, Km, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, Jl, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rl, Yaldizli, Ö, Vécsei, L, Kieseier, Bc, Hartung, Hp, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, Lm, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintoré, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, Sv., Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Dalla Costa, G., Runia, T., Evdoshenko, E., Thouvenot, E., Trojano, M., Norgren, N., Teunissen, C., Kappos, L., Giovannoni, G., Kuhle, J., on behalf of the International ClinicallyIsolated Syndrome Study, Group, and Neurology

Subjects
Male, Pathology, Future studies, Gastroenterology, 0302 clinical medicine, Neurofilament Proteins, Multiple Sclerosi, 0303 health sciences, Clinically isolated syndrome, medicine.diagnostic_test, Medicine (all), Neurofilament Protein, Demyelinating Disease, Magnetic Resonance Imaging, Psychiatry and Mental Health, Predictive value of tests, Disease Progression, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Neurofilament light, multiple sclerosis, adult, axons, biomarkers, demyelinating diseases, disease progression, female, follow-up studies, humans, magnetic resonance imaging, male, neurofilament proteins, predictive value of tests, neurology (clinical), psychiatry and mental health, surgery, arts and humanities (miscellaneous), medicine (all), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Axon, Follow-Up Studie, 03 medical and health sciences, Arts and Humanities (miscellaneous), Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, MULTIPLE SCLEROSIS, 030304 developmental biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Biomarker, medicine.disease, Axons, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Demyelinating Diseases, Follow-Up Studies
Abstract

International audience; BACKGROUND:Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.METHODS:We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls.RESULTS:NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p = 1.5 × 10(-5) and OR = 7.03; 95% CI 2.85 to 17.34; p = 2.3 × 10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR = 2.36; 95% CI 1.21 to 4.59; p = 0.011), gadolinium-enhancing lesions (OR = 2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR = 2.54; 95% CI 1.21 to 5.31; p = 0.013) at CIS diagnosis.CONCLUSIONS:If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.

Published
2016

34. P1894Serum light-chain neurofilament is associated with brain atrophy in patients with atrial fibrillation

Author

Aeschbacher, S, primary, Meyre, P, additional, Sinnecker, T, additional, Ammann, P, additional, Auricchio, A S, additional, Kobza, R, additional, Shah, D, additional, Sticherling, C, additional, Ehret, G, additional, Kuhne, M, additional, Osswald, S, additional, Conen, D, additional, Bonati, L H, additional, Kuhle, J, additional, and Wurfel, J, additional

Published
2019
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37. Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared With Healthy Ethnicity-Matched Controls

Author

Hof, M. van den, Haneveld, M.J.K., Blokhuis, C., Scherpbier, H.J., Jansen, H.P.G., Kootstra, N.A., Dallinga-Thie, G.M., Deventer, S.J.H. van, Tsimikas, S., Pajkre, D., Cohen, S., Kuijpers, T.W., Plas, A. van der, Weijsenfeld, A., Stege, J.S. ter, Caan, M.W.A., Mutsaerts, H.J.M.M., Majoie, C.B.L.M., Deinirkaya, N., Verbraak, F.D., Schmand, B., Geurtsen, G., Mathot, R.A.A., Wit, F.W.N.M., Reiss, P., Teunissen, C.F., Kuhle, J., Meijer, J.C.M., and NOVICE Study Grp

Subjects
lipids, lipoprotein(a), lipids (amino acids, peptides, and proteins), perinatal HIV infection, cardiovascular disease risk, MRI
Abstract

Background. HIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)-treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+.Methods. We cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8-18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease- and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models.Results. PHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6-82.4] vs 21.8 [16.8-46.6] mg/dL; P = .033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV- or cART-related variables or with neuroimaging outcomes.Conclusions. cART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub) clinical CVD measurements in cART-treated PHIV+ patients.

Published
2019

38. Real-world experience with Ocrelizumab in the MSBase Registry

Author

Patti, F., Eichau, S., Alroughani, R., Terzi, M., Boz, C., Grand'Maison, F., Grammond, P., Kalincik, T., Van Pesch, V., Barnett, M., Kuhle, J., Hodgkinson, S., Skibina, O., Soysal, A., Butler, E., Slee, M., Prevost, J., Laureys, G., Macdonell, R., van Beek, J., Craveiro, L., Wormser, D., Muros-Le Rouzic, E., Lechner-Scott, J., Ozakbas, SERKAN, Butzkueven, H., and Spelman, T.

Published
2019

39. Introducing Machine Learning for full MS patient trajectories improves predictions for disability score progression

Author

Brouwer, E., Peeters, L., Becker, T., Altintas, A., Soysal, A., Wijmeersch, B., Boz, C., Oreja-Guevara, C., Gobbi, C., Solaro, C., Ramo, C., Spitaleri, D. L., Maimone, D., Aguera-Morales, E., Cartechini, E., Butler, E., Havrdova, E., Patti, F., Granella, F., Grand Maison, F., Moore, F., Verheul, F., Iuliano, G., Butzkueven, H., Lechner-Scott, J., Kuhle, J., Sanchez Menoyo, J. L., Rojas, J. I., Prevost, J., Onofrj, M., Rio, M. E., Sa, M. J., Saladino, M. L., Slee, M., Barnett, M., Terzi, M., Deri, N., Mccombe, P., Sola, P., Duquette, P., Grammond, P., Ampapa, R., Alroughani, R., Hupperts, R., Recai Turkoglu, Gouider, R., Fernandez Bolanos, R., Bergamaschi, R., Kalincik, T., and Moreau, Y.

Published
2019

41. Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study

Author

Cuello, J. P., primary, Martínez Ginés, M. L., additional, Kuhle, J., additional, García Domínguez, J. M., additional, Lozano Ros, A., additional, Romero Delgado, F., additional, Higueras, Y., additional, Meldaña Rivera, A., additional, Goicochea Briceño, H., additional, García‐Tizon Larroca, S., additional, De León-Luis, J., additional, Michalak, Z., additional, Barro, C., additional, Álvarez Lafuente, R., additional, Medina Heras, S., additional, Fernández Velasco, J. I., additional, Tejeda‐Velarde, A., additional, Domínguez‐Mozo, M. I., additional, Muriel, A., additional, de Andrés, C., additional, and Villar, L. M., additional

Published
2019
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42. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

Leurs, CE, primary, Twaalfhoven, HAM, additional, Lissenberg-Witte, BI, additional, van Pesch, V, additional, Dujmovic, I, additional, Drulovic, J, additional, Castellazzi, M, additional, Bellini, T, additional, Pugliatti, M, additional, Kuhle, J, additional, Villar, LM, additional, Alvarez-Cermeño, JC, additional, Alvarez-Lafuente, R, additional, Hegen, H, additional, Deisenhammer, F, additional, Walchhofer, LM, additional, Thouvenot, E, additional, Comabella, M, additional, Montalban, X, additional, Vécsei, L, additional, Rajda, C, additional, Galimberti, D, additional, Scarpini, E, additional, Altintas, A, additional, Rejdak, K, additional, Frederiksen, JL, additional, Pihl-Jensen, G, additional, Jensen, PEH, additional, Khalil, M, additional, Voortman, MM, additional, Fazekas, F, additional, Saiz, A, additional, La Puma, D, additional, Vercammen, M, additional, Vanopdenbosch, L, additional, Uitdehaag, BMJ, additional, Killestein, J, additional, Bridel, C, additional, and Teunissen, C, additional

Published
2019
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43. Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis.

Author

Raftopoulos, R., Kuhle, J., Grant, D., Hickman, S. J., Altmann, D. R., Leppert, D., Blennow, K., Zetterberg, H., Kapoor, R., Giovannoni, G., and Gnanapavan, S.

Subjects
*OPTIC neuritis, *CYTOPLASMIC filaments, *PHENYTOIN, *VISUAL pathways, *NERVE fibers
Abstract

Background: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. Methods: Eighty‐six acute ON cases were randomized to receive phenytoin (4–6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). Results: Sixty‐four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was −44 pg/ml at 3 months (P = 0.019) and −27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and −1.6 pg/ml at 6 months (P = 0.766). Conclusions: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized. [ABSTRACT FROM AUTHOR]

Published
2021
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45. Influence of age at disease onset on future relapses and disability progression in patients with multiple sclerosis on immunomodulatory treatment.

Author

Wyl, V., Décard, B. F., Benkert, P., Lorscheider, J., Hänni, P., Lienert, C., Kuhle, J., Derfuss, T., Kappos, L., and Yaldizli, Ö.

Subjects
AGE of onset, MULTIPLE sclerosis, PROPORTIONAL hazards models, ADOLESCENCE, EXPERIMENTAL design
Abstract

Background and purpose: To investigate the relation of age at disease onset and clinical outcomes across the lifespan from adolescence in patients with multiple sclerosis (MS) on disease‐modifying therapy (DMT). Methods: We analysed data from the Swiss Association for Joint Tasks of Health Insurers database containing data from 14 718 patients with MS. Patients were included in this analysis when they were on DMT for at least 1 year. The influence of age at disease onset on future relapses and disability worsening was explored using multivariable Cox proportional hazard regression models. Results: Data from 9705 patients with MS were analysed. Pediatric‐onset MS patients (n = 236) had higher relapse rates and marginally slower disability worsening rates compared with adult‐onset MS (n = 9469). The risk of relapses was highest in childhood and decreased continuously to about 35 years of age. It remained stable for about a decade and then again continuously decreased. In contrast, disability worsening hazards remained stable from childhood to about 32 years of age and then increased sharply around the age of 45 years. Conclusions: Age is an important factor independently affecting clinical outcomes in MS. This should be considered when designing clinical trials or choosing DMT. [ABSTRACT FROM AUTHOR]

Published
2020
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47. Neurofilament light chain: a biomarker for disease onset and survival in genetic frontotemporal dementia

Author

Meeter, L., Dopper, E., Jiskoot, L., Sanchez-Valle, R., Caroline Graff, Benussi, L., Ghidoni, R., Pijnenburg, Y., Borroni, B., Galimberti, D., Laforce, R. J., Masellis, M., Vandenberghe, R., Le Ber, I., Otto, M., Minkelen, R., Papma, J., Rombouts, S., Balasa, M., Oijerstedt, L., Jelic, V., Cash, D., Harding, S., Cardoso, M. J., Ourselin, S., Dick, K., Rossor, M., Binetti, G., Padovani, A., Scarpini, E., Fenoglio, C., Tartaglia, C., Lamari, F., Barro, C., Kuhle, J., Rohrer, J., Teunissen, C., and Swieten, J.

Published
2016

48. Real-world-Evidenz

Author

Ziemssen, T., primary, Rothenbacher, D., additional, Kuhle, J., additional, and Berger, T., additional

Published
2017
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49. Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro

Author

Bridel, C., primary, Koel-Simmelink, M. J. A., additional, Peferoen, L., additional, Derada Troletti, C., additional, Durieux, S., additional, Gorter, R., additional, Nutma, E., additional, Gami, P., additional, Iacobaeus, E., additional, Brundin, L., additional, Kuhle, J., additional, Vrenken, H., additional, Killestein, J., additional, Piersma, S. R., additional, Pham, T. V., additional, De Vries, H. E., additional, Amor, S., additional, Jimenez, C. R., additional, and Teunissen, C. E., additional

Published
2017
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50. Anti‐inflammatory disease‐modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

Author

Lorscheider, J., Kuhle, J., Izquierdo, G., Lugaresi, A., Havrdova, E., Horakova, D., Hupperts, R., Duquette, P., Girard, M., Prat, A., Grand'Maison, F., Grammond, P., Sola, P., Ferraro, D., Trojano, M., Ramo‐Tello, C., Lechner‐Scott, J., Pucci, E., Solaro, C., and Slee, M.

Subjects
*MULTIPLE sclerosis, *MEDICAL care, *CLINICAL trials, *DISEASE progression, *DEMYELINATION
Abstract

Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti‐inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti‐inflammatory disease‐modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease‐modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention‐to‐treat and an as‐treated approach in paired, pairwise‐censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on‐study pairwise‐censored follow‐up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3‐month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease‐modifying agents suggests that these therapies have no substantial effect on short‐ to medium‐term disability outcomes in PPMS. [ABSTRACT FROM AUTHOR]

Published
2019
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