Publication: Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab.
Loading...
Identifiers
Date
2019-10-29
Authors
Wiendl, Heinz
Carraro, Matthew
Comi, Giancarlo
Izquierdo, Guillermo
Kim, Ho Jin
Sharrack, Basil
Tornatore, Carlo
Daizadeh, Nadia
Chung, Luke
Jacobs, Alan K
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
To 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. Patients 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 [Treg]), and CD19+ B cells (total/immature/mature/memory) and ratios of CD19+ (total/immature/mature/memory) to Treg (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. Lymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19+ to Treg 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. Repopulation 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.
Description
MeSH Terms
Adolescent
Adult
Alemtuzumab
Autoimmune Diseases
Female
Humans
Immunologic Factors
Kidney Diseases
Lymphocyte Count
Lymphocytes
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
Recurrence
Thrombocytopenia
Thyroid Diseases
Young Adult
Adult
Alemtuzumab
Autoimmune Diseases
Female
Humans
Immunologic Factors
Kidney Diseases
Lymphocyte Count
Lymphocytes
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
Recurrence
Thrombocytopenia
Thyroid Diseases
Young Adult