Skip to main content
Top
Published in: Journal of Neurology 1/2016

01-01-2016 | Original Communication

Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series

Authors: Laura Azzopardi, Amanda L. Cox, Claire L. McCarthy, Joanne L. Jones, Alasdair J. Coles

Published in: Journal of Neurology | Issue 1/2016

Login to get access

Abstract

Alemtuzumab is an anti-CD52 monoclonal antibody recently licensed for use in relapsing–remitting multiple sclerosis. Here, we report our experience of its use in neuromyelitis optica (NMO) spectrum disorders. A retrospective case review of patients treated with alemtuzumab in Cambridge, UK, was conducted to identify those who fulfil the criteria for NMO spectrum disorder. Three cases were identified. Case 1, 9-year-old female, presented with transverse myelitis and bilateral optic neuritis, with one lower medullary and several longitudinally extensive cord lesions. Despite immunosuppression including two courses of alemtuzumab, she continued to relapse, was wheelchair bound and registered blind by age 12, and died at age 18. Case 2, 41-year-old female, presented with bilateral optic neuritis and transverse myelitis with longitudinally extensive cervical cord lesions. Despite three courses of alemtuzumab, she had five relapses with visual impairment and new cord lesions. She later developed tumefactive white matter lesions and died aged 51. Case 3, 31-year-old female, presented with transverse myelitis with longitudinally extensive cervical cord lesions and positive aquaporin-4 antibody. After one course of alemtuzumab, she relapsed with 4 episodes of myelitis with new enhancing lesions and accumulating disability. She became relapse free after rituximab and mycophenolate mofetil. From this case series, we conclude that alemtuzumab failed to prevent disabling relapses and poor outcome in NMO. We hypothesise that rituximab is more effective, as in case 3, because it causes much more prolonged B lymphocyte depletion than alemtuzumab. We therefore caution against the use of alemtuzumab in NMO.
Literature
1.
go back to reference Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ (2005) Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 35(11):3332–3342. doi:10.1002/eji.200535075 CrossRefPubMed Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ (2005) Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 35(11):3332–3342. doi:10.​1002/​eji.​200535075 CrossRefPubMed
2.
go back to reference Jones JL, Thompson SAJ, Loh P, Davies JL, Tuohy OC, Curry AJ, Azzopardi L, Hill-Cawthorne G, Fahey MT, Compston A, Coles AJ (2013) Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc Natl Acad Sci. doi:10.1073/pnas.1313654110 Jones JL, Thompson SAJ, Loh P, Davies JL, Tuohy OC, Curry AJ, Azzopardi L, Hill-Cawthorne G, Fahey MT, Compston A, Coles AJ (2013) Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc Natl Acad Sci. doi:10.​1073/​pnas.​1313654110
3.
go back to reference Hill-Cawthorne GA, Button T, Tuohy O, Jones JL, May K, Somerfield J, Green A, Giovannoni G, Compston DA, Fahey MT, Coles AJ (2012) Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 83(3):298–304. doi:10.1136/jnnp-2011-300826 CrossRefPubMed Hill-Cawthorne GA, Button T, Tuohy O, Jones JL, May K, Somerfield J, Green A, Giovannoni G, Compston DA, Fahey MT, Coles AJ (2012) Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 83(3):298–304. doi:10.​1136/​jnnp-2011-300826 CrossRefPubMed
4.
go back to reference Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA (2012) Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology 78(14):1069–1078. doi:10.1212/WNL.0b013e31824e8ee7 CrossRefPubMed Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA (2012) Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology 78(14):1069–1078. doi:10.​1212/​WNL.​0b013e31824e8ee7​ CrossRefPubMed
5.
go back to reference Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung H-P, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DAS (2012) Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing–remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 380:1819–1828CrossRefPubMed Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung H-P, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DAS (2012) Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing–remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 380:1819–1828CrossRefPubMed
6.
go back to reference Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380(9856):1829–1839. doi:10.1016/s0140-6736(12)61768-1 CrossRefPubMed Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380(9856):1829–1839. doi:10.​1016/​s0140-6736(12)61768-1 CrossRefPubMed
7.
go back to reference Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112. doi:10.1016/s0140-6736(04)17551-x CrossRefPubMed Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112. doi:10.​1016/​s0140-6736(04)17551-x CrossRefPubMed
8.
go back to reference Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T (2014) The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol (Zurich, Switzerland) 24(1):83–97. doi:10.1111/bpa.12099 CrossRef Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T (2014) The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol (Zurich, Switzerland) 24(1):83–97. doi:10.​1111/​bpa.​12099 CrossRef
10.
go back to reference Wingerchuk D, Banwell B, Bennett J, Cabre P, Carroll W, Chitnis T, De Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon J, Tenembaum S, Traboulsee A, Waters P, Wellik K, Weinshenker B (2014) Revised diagnostic criteria for neuromyelitis optica spectrum disorders (S63.001). Neurology 82(10 Suppl):S63.001 Wingerchuk D, Banwell B, Bennett J, Cabre P, Carroll W, Chitnis T, De Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon J, Tenembaum S, Traboulsee A, Waters P, Wellik K, Weinshenker B (2014) Revised diagnostic criteria for neuromyelitis optica spectrum disorders (S63.001). Neurology 82(10 Suppl):S63.001
13.
go back to reference Kieseier BC, Stuve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, Ringelstein M, Turowski B, Aktas O, Antoch G, Hartung HP (2013) Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol 70(3):390–393. doi:10.1001/jamaneurol.2013.668 CrossRefPubMed Kieseier BC, Stuve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, Ringelstein M, Turowski B, Aktas O, Antoch G, Hartung HP (2013) Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol 70(3):390–393. doi:10.​1001/​jamaneurol.​2013.​668 CrossRefPubMed
Metadata
Title
Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series
Authors
Laura Azzopardi
Amanda L. Cox
Claire L. McCarthy
Joanne L. Jones
Alasdair J. Coles
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 1/2016
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7925-y

Other articles of this Issue 1/2016

Journal of Neurology 1/2016 Go to the issue