RT Journal Article
SR Electronic
T1 Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e635
DO 10.1212/NXI.0000000000000635
VO 7
IS 1
A1 Heinz Wiendl
A1 Matthew Carraro
A1 Giancarlo Comi
A1 Guillermo Izquierdo
A1 Ho Jin Kim
A1 Basil Sharrack
A1 Carlo Tornatore
A1 Nadia Daizadeh
A1 Luke Chung
A1 Alan K. Jacobs
A1 Richard J. Hogan
A1 Linda V. Wychowski
A1 Bart Van Wijmeersch
A1 ,
YR 2020
UL http://nn.neurology.org/content/7/1/e635.abstract
AB Objective 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.Methods 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.Results 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.Conclusions 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.AE=adverse event; Breg=regulatory B; CARE-MS=Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CDW=confirmed disability worsening; EDSS=Expanded Disability Status Scale; MMRM=mixed-effects model for repeated measures; NEDA=no evidence of disease activity; RRMS=relapsing-remitting MS; Treg=regulatory T