PMID- 31662412
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20210215
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 7
IP  - 1
DP  - 2020 Jan
TI  - Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy 
      after alemtuzumab.
LID - 10.1212/NXI.0000000000000635 [doi]
LID - e635
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 [T(reg)]), and CD19(+) B cells 
      (total/immature/mature/memory) and ratios of CD19(+) 
      (total/immature/mature/memory) to T(reg) (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 
      T(reg) 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.
CI  - Copyright (c) 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Wiendl, Heinz
AU  - Wiendl H
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium. heinz.wiendl@ukmuenster.de.
FAU - Carraro, Matthew
AU  - Carraro M
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Comi, Giancarlo
AU  - Comi G
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Izquierdo, Guillermo
AU  - Izquierdo G
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Kim, Ho Jin
AU  - Kim HJ
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Sharrack, Basil
AU  - Sharrack B
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Tornatore, Carlo
AU  - Tornatore C
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Daizadeh, Nadia
AU  - Daizadeh N
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Chung, Luke
AU  - Chung L
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Jacobs, Alan K
AU  - Jacobs AK
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Hogan, Richard J
AU  - Hogan RJ
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Wychowski, Linda V
AU  - Wychowski LV
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
FAU - Van Wijmeersch, Bart
AU  - Van Wijmeersch B
AD  - From the University of Munster (H.W.), Munster, Germany; Novant Health (M.C.), 
      Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen 
      Macarena University Hospital (G.I.), Seville, Spain; Research Institute and 
      Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield 
      Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield 
      (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), 
      Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific 
      Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions 
      (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), 
      BIOMED, Hasselt University, Hasselt, Belgium.
CN  - CARE-MS I, CARE-MS II, and CAMMS03409 Investigators
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191029
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
RN  - 0 (Immunologic Factors)
RN  - 3A189DH42V (Alemtuzumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alemtuzumab/administration & dosage/adverse effects/*pharmacology
MH  - Autoimmune Diseases/*chemically induced
MH  - Female
MH  - Humans
MH  - Immunologic Factors/administration & dosage/adverse effects/*pharmacology
MH  - Kidney Diseases/*chemically induced
MH  - Lymphocyte Count
MH  - Lymphocytes/*drug effects
MH  - Male
MH  - Middle Aged
MH  - *Multiple Sclerosis, Relapsing-Remitting/blood/drug therapy/physiopathology
MH  - Recurrence
MH  - Thrombocytopenia/*chemically induced
MH  - Thyroid Diseases/*chemically induced
MH  - Young Adult
PMC - PMC6865853
EDAT- 2019/10/31 06:00
MHDA- 2021/02/16 06:00
PMCR- 2019/10/29
CRDT- 2019/10/31 06:00
PHST- 2019/05/15 00:00 [received]
PHST- 2019/09/05 00:00 [accepted]
PHST- 2019/10/31 06:00 [entrez]
PHST- 2019/10/31 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2019/10/29 00:00 [pmc-release]
AID - 7/1/e635 [pii]
AID - NEURIMMINFL2019021477 [pii]
AID - 10.1212/NXI.0000000000000635 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2019 Oct 29;7(1):e635. doi: 
      10.1212/NXI.0000000000000635. Print 2020 Jan.