Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking.

Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies.

Design: Case study.

Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA.

Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories.

Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Keywords: apheresis; aquaporin-4; case report; immunotherapy; neuromyelitis optica spectrum disorder.

Figure 1.

Timeline with relevant data of events and interventions before and with maintenance tryptophan immunoadsorption (Tr-IA) in two cases with severe NMOSD. EDSS, expanded disability status scale; FSS, functional system score; Glat, glatirameracetate; IVIG, intravenous immunoglobulin; Mitox, mitoxantron; R, right eye; Ritux, rituximab; TCZ, Tocilizumab; Tr-IA, tryptophan immunoadsorption; VA, visual acuity; VF, visual function.

Figure 2.

MRI imaging of a 52-year-old female patient with AQP4-IgG-seropositive NMOSD (case 1): (a) T2-weighted sagittal and axial spinal cord imaging revealing a new lesion at Th6 (arrow) before start of Tr-IA maintenance therapy and (b) after 2.5 years of Tr-IA therapy stable disease without new spinal lesion.

Figure 3.

MRI imaging of a 49-year-old woman with AQP4-IgG-seronegative NMOSD (case 2). (a) T2-weighted sagittal and axial spinal cord imaging revealing an LETM extending from T2 to T4 (arrow), associated with acute myelitis, 6 years after onset of disease. (b) Sagittal STIR- and axial T1-gadolinium-enhanced images 10 years after disease onset showing acute cervical myelitis and widespread lesions in the entire spinal cord. (c) Axial T2-weighted and T1-gadolinium-enhanced images 11 years after disease onset and before start of Tr-IA maintenance therapy. (d) After 2 years of maintenance therapy with Tr-IA, almost complete regression of spinal lesion load on T-weighted sagittal and axial images is seen.