RT Journal Article
T1 Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab.
A1 Wiendl, Heinz
A1 Carraro, Matthew
A1 Comi, Giancarlo
A1 Izquierdo, Guillermo
A1 Kim, Ho Jin
A1 Sharrack, Basil
A1 Tornatore, Carlo
A1 Daizadeh, Nadia
A1 Chung, Luke
A1 Jacobs, Alan K
A1 Hogan, Richard J
A1 Wychowski, Linda V
A1 Van Wijmeersch, Bart
A1 CARE-MS I, CARE-MS II, and CAMMS03409 Investigators
AB 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.
YR 2019
FD 2019-10-29
LK http://hdl.handle.net/10668/15511
UL http://hdl.handle.net/10668/15511
LA en
DS RISalud
RD Apr 11, 2025