Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series
- 682 Downloads
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.
KeywordsAlemtuzumab Neuromyelitis optica Multiple sclerosis Neuroimmunology
Clinical work is performed at the Wellcome Clinical Research Facility. JLJ and AJC are supported by the Cambridge Biomedical Research Centre of the National Institute for Health Research.
Compliance with ethical standards
Conflicts of interest
JLJ reports receiving consulting fees and lecture fees from Genzyme Sanofi. AJC reports receiving consulting fees, lecture fees and institutional grant support from Genzyme Sanofi. LA, ALC and CMC declare they have no conflict of interest.
All patients provided informed consent to alemtuzumab treatment and long-term follow-up at Addenbrooke’s Hospital, Cambridge, UK.
- 3.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 CrossRefPubMedGoogle Scholar
- 4.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 CrossRefPubMedGoogle Scholar
- 5.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 380:1819–1828CrossRefPubMedGoogle Scholar
- 6.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 CrossRefPubMedGoogle Scholar
- 10.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):S63.001Google Scholar
- 11.Wang KC, Lin KH, Lee TC, Lee CL, Chen SY, Chen SJ, Chin LT, Tsai CP (2014) Poor responses to interferon-beta treatment in patients with neuromyelitis optica and multiple sclerosis with long spinal cord lesions. PLoS One 9(6):e98192. doi: 10.1371/journal.pone.0098192 PubMedCentralCrossRefPubMedGoogle Scholar
- 13.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 CrossRefPubMedGoogle Scholar