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Original Contributions |

Failure of Natalizumab to Prevent Relapses in Neuromyelitis Optica

Ingo Kleiter, MD; Kerstin Hellwig, MD; Achim Berthele, MD; Tania Kümpfel, MD; Ralf A. Linker, MD; Hans-Peter Hartung, MD; Friedemann Paul, MD; Orhan Aktas, MD; for the Neuromyelitis Optica Study Group
Arch Neurol. 2012;69(2):239-245. doi:10.1001/archneurol.2011.216.
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Objective To describe first experiences with the integrin inhibitor natalizumab, given to patients with suspected relapsing-remitting multiple sclerosis (MS) who were later diagnosed with aquaporin 4–positive neuromyelitis optica (NMO).

Design Retrospective case series.

Setting Neurology departments at tertiary referral centers in Germany.

Patients Patients with NMO who tested positive for antibodies to aquaporin 4.

Intervention Treatment with natalizumab.

Main Outcome Measures Relapses and accumulation of disability.

Results We identified 5 patients (4 female; median age, 45 years) who were initially diagnosed with MS and treated with natalizumab before diagnosis of NMO was established. Natalizumab was given as escalation therapy after failure of first- or second-line immunomodulatory therapies for MS. During natalizumab therapy (median duration, 8 infusions; range, 2-11 infusions), all 5 patients displayed persisting disease activity; a total of 9 relapses occurred (median duration to relapse, 120 days; range, 45-230 days) after the start of treatment. Four patients had an accumulation of disability and 1 patient died 2 months after cessation of natalizumab treatment.

Conclusions Our results suggest that natalizumab fails to control disease activity in patients with NMO. Neuromyelitis optica should be considered as a differential diagnosis in patients with suspected MS who are unresponsive to natalizumab therapy.

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Figure. Relapses in patients with neuromyelitis optica before, during, and after treatment with natalizumab. Shown are all relapses (diamonds) from day −400 to +400 relative to start of medication. Bars depict duration of natalizumab treatment until plasma exchange (patients 1, 2, and 5) or 4 weeks after last infusion (patients 3 and 4).

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