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http://hdl.handle.net/1942/31369
Title: | Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab | Authors: | Wiendl, Heinz Carraro, Matthew Comi, Giancarlo Izquierdo, Guillermo Kim, Ho Jin Sharrack, Basil Tornatore, Carlo Daizadeh, Nadia Chung, Luke Jacobs, Alan K. Hogan, Richard J. Wychowski, Linda V. VAN WIJMEERSCH, Bart |
Issue Date: | 2020 | Publisher: | LIPPINCOTT WILLIAMS & WILKINS | Source: | NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION, 7 (1) | Abstract: | ObjectiveTo examine the association between peripheral blood lymphocyte pharmacodynamics and autoimmune adverse events (AEs) or return of disease activity in alemtuzumab-treated patients with relapsing-remitting MS.MethodsPatients received 2 alemtuzumab courses (12 mg/d IV; 5 days at baseline, 3 days 12 months later) in the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis studies (NCT00530348 and NCT00548405) and could then receive as-needed alemtuzumab or other disease-modifying therapy in a 4-year extension (NCT00930553). Lymphocytes were phenotyped quarterly over 2 years using fluorescence-activated cell sorting. Pharmacodynamic assessments included counts of total lymphocytes, CD3(+) T cells, CD4(+)/CD8(+) T cells (total/naive/memory/regulatory [T-reg]), and CD19(+) B cells (total/immature/mature/memory) and ratios of CD19(+) (total/immature/mature/memory) to T-reg (CD4(+)/CD8(+)) counts. Assessed autoimmune AEs included immune thrombocytopenia, nephropathies, and thyroid events. Efficacy assessments included relapses, 6-month confirmed disability worsening (CDW), and MRI disease activity.ResultsLymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19(+) to T-reg cell count ratios), showed no significant differences over 2 years in patients developing/not developing autoimmune AEs, relapses, CDW, or MRI activity through 6 years following alemtuzumab. Lymphocyte kinetics were also unrelated to multiple autoimmune AEs or extreme clinical phenotypes.ConclusionsRepopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response. | Notes: | Wiendl, H (reprint author), Univ Munster, Munster, Germany. heinz.wiendl@ukmuenster.de |
Other: | Wiendl, H (corresponding author), Univ Munster, Munster, Germany. heinz.wiendl@ukmuenster.de | Keywords: | Remitting Multiple-Sclerosis;Depletion;Therapy;Update;Cells | Document URI: | http://hdl.handle.net/1942/31369 | ISSN: | 2332-7812 | e-ISSN: | 2332-7812 | DOI: | 10.1212/NXI.0000000000000635 | ISI #: | WOS:000530690100003 | Rights: | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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