Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders

Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders

The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects. Neurological assessment including the determination of the Expanded Disability Status Scale (EDSS) score and ophthalmologic evaluations were performed every 3 months and during relapses. Flow cytometric analysis, brain and spinal cord MRI was performed at baseline, 6, 12, 18, and 24 months.

Inclusion Criteria:

• Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without recurrent ON (unilateral or bilateral) but with normal brain MRI and positive serological NMO IgG antibody.
• Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without spatially limited brain lesion and positive serological NMO IgG antibody.
• NMO, fulfilled Wingerchuk 2006 Criteria for NMO.
• Patient presented at least 2 relapses during the 12 months preceding the start of mitoxantrone therapy, despite immunotherapies using corticosteroid, interferon beta, azathioprine, cyclophosphamide, Cyclosporin A, Mycophenolate Mofetil or a combination of these drugs
• Extended Disability Status Score 3-8.
• Normal range for white-blood-cell count (more than 4×109/L), neutrophil count (more than 2×109/L), and platelet count (more than 100×109/L).

Exclusion Criteria:

• Cardiac risk factors (e.g history of congestive heart failure and left ventricular ejection fraction (LVEF) < 50%
• Systemic diseases such as lupus, Sjogren's syndrome, anti-phospholipid antibody syndrome, sarcoidosis, rheumatoid arthritis, or vitamin B12 deficiency
• Previous treatment with mitoxantrone or anthracyclines
• Pregnant or planning to be pregnant
• Patients with severe liver disorders (WHO grade 4)