401 General Military Hospital of Athens
Neurology

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0352 - Lymphocyte Subtypes Repopulation Pattern and Secondary Autoimmunity in patients with RRMS treated with Alemtuzumab in a Real World setting (ID 1112)

Speakers
Presentation Number
P0352
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Alemtuzumab is a humanized monoclonal antibody targeting CD52 expressing T and B lymphocytes used as a second line treatment for patients with highly active Relapsing Remitting Multiple Sclerosis (RRMS). Treatment with alemtuzumab has been associated with increased incidence of secondary auto-immune adverse events. Although the exact underlying mechanisms remain unclear, it has been hypothesized that secondary auto-immunity is a result of the fast / excessive repopulation of autoreactive CD19 lymphocytes following their initial depletion.

Objectives

To investigate the potential association of peripheral lymphocyte subtypes kinetics following treatment with Αlemtuzumab with auto-immune adverse events as well as with disease activity and disease progression in patients with RRMS, in a real-world setting.

Methods

Α retrospective analysis of data from a series of 33 patients that received two courses of treatment and completed at least 24 months of follow up was performed. Primary endpoints included incidence of new or exacerbation of preexisting auto-immunities, disease activity and disease progression in association with lymphocyte depletion and repopulation patterns. Lymphocyte subpopulations (CD4+/CD8+ T cells, CD19+ B cells total and memory, CD56 NK cells) were measured using flow cytometry at baseline and at months one, three, six and twelve after each treatment course. Patients were assessed clinically and with MRI every six months throughout the 2-year follow-up period. Statistical analysis included generalized linear models for repeated measures.

Results

Overall, 17 adverse events of autoimmune origin and 2 cases of exacerbation of previously existing auto-immunities were observed. Lymphocyte repopulation patterns did not show significant differences in association with incidence of auto-immune reactions. Repopulation kinetics were also unrelated to any other primary outcome investigated in this study.

Conclusions

Our findings suggest that lymphocytes repopulation patterns do not have a predictive value of the incidence of secondary auto-immunity, as well as the activity and the progression of the disease, following treatment with Alemtuzumab. The mechanisms behind the differentiation among patients in regards to autoimmune reactions may lie in more specific lymphocyte subpopulations that have not been included in this study or in deeper molecular paths mediated by specific cytokines. Further study is required in this field.

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