A five-year observational prospective mono-center study of the efficacy of alemtuzumab in a real-world cohort of patients with multiple sclerosis.

Autor:	Sandgren S; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden., Novakova L; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden., Nordin A; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden., Axelsson M; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden., Malmeström C; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.; Laboratory for Clinical Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, University College London (UCL) Queen Square Institute of Neurology, London, United Kingdom.; UK Dementia Research Institute at University College London (UCL), London, United Kingdom.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, Hong Kong SAR, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States., Lycke J; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2023 Sep 21; Vol. 14, pp. 1265354. Date of Electronic Publication: 2023 Sep 21 (Print Publication: 2023).
DOI:	10.3389/fneur.2023.1265354
Abstrakt:	Background: Alemtuzumab (ALZ) is a pulsed immune reconstitution therapy for multiple sclerosis (MS). Objective: To assess basic characteristics, therapeutic effects, and prognostic biomarkers on clinical and imaging parameters of disease activity for relapsing-remitting MS (RRMS) patients selected for ALZ, in a real-world long-term setting. Methods: Fifty-one RRMS patients [female = 31; mean age 36 (standard deviation 7.1) years; median expanded disability status scale (EDSS) 2 (interquartile range (IQR) 1.5)] initiating ALZ treatment, were consecutively included. Patients were assessed at baseline and thereafter annually for 5 years with clinical measures, symbol digit modality test (SDMT), and magnetic resonance imaging (MRI). Concentrations of glial fibrillary acidic protein (GFAP), reflecting astrogliosis, and neurofilament light (NfL), reflecting axonal damage, were measured in cerebrospinal fluid (CSF) and serum samples collected at baseline and after 2 years in CSF, and annually in serum. Control subjects were symptomatic controls (SCs, n  = 27), who were examined at baseline and after 5 years without evidence of neurological disease. Results: While the mean annualized relapse rate was significantly reduced from baseline at each year of follow-up, disability was essentially maintained at a median EDSS of 1.5 and IQR between 1.13 and 2.25. New MRI activity was recorded in 26 patients (53%) over 5 years. The proportion of patients who achieved no evidence of disease activity (NEDA-3), 6-months confirmed disability worsening (CDW), and 6-months confirmed disability improvement (CDI) at 5 years were 33, 31, and 31%, respectively. The SDMT score was reduced for patients ( p  < 0.001), but unchanged for SCs. ALZ treatment did not change GFAP levels, whereas there was a significant decrease for RRMS patients in median CSF and serum NfL levels at follow-up [CSF month 24: 456 pg./mL (IQR 285.4) ( p  = 0.05); serum month 24: 6.7 pg/mL (IQR 4.7) ( p  < 0.01); serum month 60: 7.2 pg/mL (IQR 4.7) ( p  < 0.01)], compared to baseline [CSF: 1014 pg/mL (IQR 2832.5); serum 8.6 pg/mL (IQR 17.4)]. Conclusion: In this real-world mono-center population, we observed a progression-free survival of 69%, cumulative NEDA-3 of 33%, and reduced NfL levels, over a five-year follow-up. This confirms ALZ as an effective pulsed immune reconstitution therapy that significantly reduces neuro axonal loss, and therefore has the potential to reduce long-term neurological disability. ALZ did not appear to affect astrogliosis. Competing Interests: SS has received compensation for lectures and/or advisory board membership from Merck. LN has received lecture honoraria from Biogen, Novartis, Teva, Sanofi and has served on advisory boards for Merck, Janssen and Sanofi. MA has received compensation for lectures and/or advisory boards from Biogen, Genzyme, and Novartis. CM has received honoraria for lectures and advisory board memberships from Biogen, Merck, Novartis, and SanofiAventis. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB BBS, which is a part of the GU Ventures Incubator Program outside submitted work. JL has received travel support and/or lecture honoraria and has served on scientific advisory boards for Alexion, Almirall, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; and has received unconditional research grants from Biogen and Novartis, and financial support from Sanofi for an investigator-initiated study. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sandgren, Novakova, Nordin, Axelsson, Malmeström, Zetterberg and Lycke.)
Databáze:	MEDLINE
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