PT  - JOURNAL ARTICLE
AU  - Heinz Wiendl
AU  - Matthew Carraro
AU  - Giancarlo Comi
AU  - Guillermo Izquierdo
AU  - Ho Jin Kim
AU  - Basil Sharrack
AU  - Carlo Tornatore
AU  - Nadia Daizadeh
AU  - Luke Chung
AU  - Alan K. Jacobs
AU  - Richard J. Hogan
AU  - Linda V. Wychowski
AU  - Bart Van Wijmeersch
ED  - ,
TI  - Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab
AID  - 10.1212/NXI.0000000000000635
DP  - 2020 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e635
VI  - 7
IP  - 1
4099  - http://nn.neurology.org/content/7/1/e635.short
4100  - http://nn.neurology.org/content/7/1/e635.full
SO  - Neurol Neuroimmunol Neuroinflamm2020 Jan 01; 7
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