Onajite Kousin-Ezewu1, Laura Azzopardi1, Richard A Parker1, Orla Tuohy1, Alastair Compston1, Alasdair Coles1, Joanne Jones2. 1. 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. 2. 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.
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: B W van Oosten; M Lai; S Hodgkinson; F Barkhof; D H Miller; I F Moseley; A J Thompson; P Rudge; A McDougall; J G McLeod; H J Adèr; C H Polman Journal: Neurology Date: 1997-08 Impact factor: 9.910
Authors: A J Coles; E Fox; A Vladic; S K Gazda; V Brinar; K W Selmaj; A Skoromets; I Stolyarov; A Bass; H Sullivan; D H Margolin; S L Lake; S Moran; J Palmer; M S Smith; D A S Compston Journal: Neurology Date: 2012-03-21 Impact factor: 9.910
Authors: Grant A Hill-Cawthorne; Tom Button; Orla Tuohy; Joanne L Jones; Karen May; Jennifer Somerfield; Alison Green; Gavin Giovannoni; D Alastair S Compston; Michael T Fahey; Alasdair J Coles Journal: J Neurol Neurosurg Psychiatry Date: 2011-11-05 Impact factor: 10.154
Authors: Amanda L Cox; Sara A J Thompson; Joanne L Jones; Vicki H Robertson; Geoff Hale; Herman Waldmann; D Alastair S Compston; Alasdair J Coles Journal: Eur J Immunol Date: 2005-11 Impact factor: 5.532
Authors: Jeffrey A Cohen; Alasdair J Coles; Douglas L Arnold; Christian Confavreux; Edward J Fox; Hans-Peter Hartung; Eva Havrdova; Krzysztof W Selmaj; Howard L Weiner; Elizabeth Fisher; Vesna V Brinar; Gavin Giovannoni; Miroslav Stojanovic; Bella I Ertik; Stephen L Lake; David H Margolin; Michael A Panzara; D Alastair S Compston Journal: Lancet Date: 2012-11-01 Impact factor: 79.321
Authors: Alasdair J Coles; Cary L Twyman; Douglas L Arnold; Jeffrey A Cohen; Christian Confavreux; Edward J Fox; Hans-Peter Hartung; Eva Havrdova; Krzysztof W Selmaj; Howard L Weiner; Tamara Miller; Elizabeth Fisher; Rupert Sandbrink; Stephen L Lake; David H Margolin; Pedro Oyuela; Michael A Panzara; D Alastair S Compston Journal: Lancet Date: 2012-11-01 Impact factor: 79.321
Authors: A J Coles; M G Wing; P Molyneux; A Paolillo; C M Davie; G Hale; D Miller; H Waldmann; A Compston Journal: Ann Neurol Date: 1999-09 Impact factor: 10.422
Authors: Alasdair J Coles; D Alastair S Compston; Krzysztof W Selmaj; Stephen L Lake; Susan Moran; David H Margolin; Kim Norris; P K Tandon Journal: N Engl J Med Date: 2008-10-23 Impact factor: 91.245
Authors: Joanne L Jones; Sara A J Thompson; Priscilla Loh; Jessica L Davies; Orla C Tuohy; Allison J Curry; Laura Azzopardi; Grant Hill-Cawthorne; Michael T Fahey; Alastair Compston; Alasdair J Coles Journal: Proc Natl Acad Sci U S A Date: 2013-11-26 Impact factor: 11.205
Authors: Mark D Willis; Trevor P Pickersgill; Neil P Robertson; Richard W J Lee; Andrew D Dick; Ester Carreño Journal: Int Ophthalmol Date: 2016-10-11 Impact factor: 2.031
Authors: David Baker; Samuel S Herrod; Cesar Alvarez-Gonzalez; Gavin Giovannoni; Klaus Schmierer Journal: JAMA Neurol Date: 2017-08-01 Impact factor: 18.302
Authors: Nicolas Dubuisson; David Baker; Angray S Kang; Gareth Pryce; Monica Marta; Leo H Visser; Werner E Hofmann; Sharmilee Gnanapavan; Gavin Giovannoni; Klaus Schmierer Journal: Immunology Date: 2018-01-04 Impact factor: 7.397