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Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab

Journal Contribution - Journal Article

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.
Journal: Neurology-Neuroimmunology & Neuroinflammation
ISSN: 2332-7812
Issue: 1
Volume: 7
Publication year:2020
Keywords:Remitting Multiple-Sclerosis, Depletion, Therapy, Update, Cells
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:10
CSS-citation score:3
Authors:International
Authors from:Higher Education
Accessibility:Open