Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis

Abstract

BackgroundIn multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established.MethodsWe prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients’ sera.ResultsAfter the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.ConclusionsIA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.

Therapeutic Apheresis in Pediatric Patients with Acute CNS Inflammatory Demyelinating Disease

“…Visual acuity of 3 eyes even decreased initially; however, an improvement in the months following apheresis was seen in all patients. Such a delayed effect of PE was not seen in a study on adult patients with ON [22], but it has been reported in IA [4,23]. However, ongoing evaluations on adults treated with either PE or IA in our center seem to show that this delayed effect is not dependent on the applied procedure [Mühlhausen et al, manuscript in preparation].…”

“…Two randomized sham-controlled studies have shown a beneficial effect of plasma exchange (PE) in adult patients with acute CNS demyelinating diseases failing to respond to treatment with ACTH or high-dose corticosteroids, respectively [2,3]. Additionally, one uncontrolled prospective study [4] and several case series [5,6] have shown comparable effects of immunoadsorption (IA) in such cases. The International Pediatric Multiple Sclerosis (MS) Study Group states: ‘Children with severe relapses not improving after high-dose IVMP pulse or with contraindications to glucocorticosteroids might benefit from a treatment with plasma exchange' [7].…”

Pediatric optic neuritis

“…Cases series have reported benefit with TPE and immunoadsorption in acute ON in adults. 42,43 Likewise, case series suggest that plasmapheresis is safe in pediatric demyelination 44 and has potential benefit in steroid-resistant pediatric ON. 45 Although some observational studies suggested a possible benefit to the use of IVIg in corticosteroid-refractory acute ON in adults, 46 a double-blind trial showed no difference between outcomes when comparing IVIg and placebo in acute ON.…”

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

“…In some countries, immunoadsorption (IA), a method to remove immunoglobulins from the circulation by adsorption to either tryptophan or protein A, is used as an alternative to TPE for the treatment of exacerbations of MS and NMOSD [46,47]. Several adult and pediatric cases have been reported in whom NMOSD attacks were successfully treated with IA [33,46,[48][49][50].…”