Cargando…

Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence

Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte su...

Descripción completa

Detalles Bibliográficos
Autores principales: Signoriello, Elisabetta, Lus, Giacomo, Saccà, Francesco, Puthenparampil, Marco, Coppola, Cinzia, Di Pietro, Andrea, Puoti, Gianfranco, Criscuolo, Maria Cristina, Foschi, Matteo, Miele, Giuseppina, Abbadessa, Gianmarco, Brescia Morra, Vincenzo, Gallo, Paolo, Bonavita, Simona, Sormani, Maria Pia, Signori, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002781/
https://www.ncbi.nlm.nih.gov/pubmed/36902555
http://dx.doi.org/10.3390/jcm12051768
_version_ 1784904458807803904
author Signoriello, Elisabetta
Lus, Giacomo
Saccà, Francesco
Puthenparampil, Marco
Coppola, Cinzia
Di Pietro, Andrea
Puoti, Gianfranco
Criscuolo, Maria Cristina
Foschi, Matteo
Miele, Giuseppina
Abbadessa, Gianmarco
Brescia Morra, Vincenzo
Gallo, Paolo
Bonavita, Simona
Sormani, Maria Pia
Signori, Alessio
author_facet Signoriello, Elisabetta
Lus, Giacomo
Saccà, Francesco
Puthenparampil, Marco
Coppola, Cinzia
Di Pietro, Andrea
Puoti, Gianfranco
Criscuolo, Maria Cristina
Foschi, Matteo
Miele, Giuseppina
Abbadessa, Gianmarco
Brescia Morra, Vincenzo
Gallo, Paolo
Bonavita, Simona
Sormani, Maria Pia
Signori, Alessio
author_sort Signoriello, Elisabetta
collection PubMed
description Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.
format Online
Article
Text
id pubmed-10002781
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100027812023-03-11 Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence Signoriello, Elisabetta Lus, Giacomo Saccà, Francesco Puthenparampil, Marco Coppola, Cinzia Di Pietro, Andrea Puoti, Gianfranco Criscuolo, Maria Cristina Foschi, Matteo Miele, Giuseppina Abbadessa, Gianmarco Brescia Morra, Vincenzo Gallo, Paolo Bonavita, Simona Sormani, Maria Pia Signori, Alessio J Clin Med Article Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure. MDPI 2023-02-22 /pmc/articles/PMC10002781/ /pubmed/36902555 http://dx.doi.org/10.3390/jcm12051768 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Signoriello, Elisabetta
Lus, Giacomo
Saccà, Francesco
Puthenparampil, Marco
Coppola, Cinzia
Di Pietro, Andrea
Puoti, Gianfranco
Criscuolo, Maria Cristina
Foschi, Matteo
Miele, Giuseppina
Abbadessa, Gianmarco
Brescia Morra, Vincenzo
Gallo, Paolo
Bonavita, Simona
Sormani, Maria Pia
Signori, Alessio
Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title_full Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title_fullStr Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title_full_unstemmed Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title_short Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
title_sort alemtuzumab-related lymphocyte subset dynamics and disease activity or autoimmune adverse events: real-world evidence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002781/
https://www.ncbi.nlm.nih.gov/pubmed/36902555
http://dx.doi.org/10.3390/jcm12051768
work_keys_str_mv AT signorielloelisabetta alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT lusgiacomo alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT saccafrancesco alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT puthenparampilmarco alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT coppolacinzia alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT dipietroandrea alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT puotigianfranco alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT criscuolomariacristina alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT foschimatteo alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT mielegiuseppina alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT abbadessagianmarco alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT bresciamorravincenzo alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT gallopaolo alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT bonavitasimona alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT sormanimariapia alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence
AT signorialessio alemtuzumabrelatedlymphocytesubsetdynamicsanddiseaseactivityorautoimmuneadverseeventsrealworldevidence