Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.
OBJECTIVE
To test the hypothesis that accelerated peripheral blood mononuclear cell recovery after alemtuzumab treatment of multiple sclerosis is associated with recurrent disease activity and to investigate the claim that CD4 counts greater than 388.5 × 10(6) cells/mL at 12 months can be used to identify patients who may benefit from further treatment.


METHODS
A total of 108 patients were followed for a median of 99 months post alemtuzumab. Patients were classified as active or nonactive after each cycle of treatment based on clinical relapse, increasing disability, or new T2/enhancing MRI lesions. These outcomes were correlated with CD4, CD8, CD19, CD56+ NK, and monocyte counts.


RESULTS
Of 108 patients, 56 (52%) relapsed at some point during follow-up. Mean annualized relapse rate after alemtuzumab was 0.17 vs 1.67 prior to treatment (equating to a 90% reduction). Of 108 patients, 28 (26%) met the criteria for sustained accumulation of disability. Median time to the lower limit of normal for CD19, CD8, and CD4 was 3, 19.5, and 32 months, respectively. There was no significant difference in the recovery of any cell population between patients with and without disease activity or accumulation of disability after treatment.


CONCLUSIONS
This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab.
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Onajite
O
Kousin-Ezewu
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Laura
L
Azzopardi
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Richard A
RA
Parker
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Orla
O
Tuohy
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Alastair
A
Compston
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK.
Alasdair
A
Coles
From the Department of Clinical Neurosciences (O.K.-E., L.A., O.T., A. Compston, A. Coles, J.J.) and the Centre for Applied Medical Statistics, Department of Public Health and Primary Care (R.A.P.), University of Cambridge, UK. jls53@medschl.cam.ac.uk.
Joanne
J
Jones
D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D055502:Secondary Prevention; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D007155:Immunologic Factors; D000074323:Alemtuzumab