Rituximab in children with myelin oligodendrocyte glycoprotein antibody and relapsing neuroinflammatory disease

Abstract

ABBREVIATIONS IVIGIntravenous immunoglobulin MOG Myelin oligodendrocyte glycoproteinThe aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population.Myelin oligodendrocyte glycoprotein (MOG) antibodies are seen in the serum of 25% to 58% of children who present with a first acquired demyelinating syndrome, 1-5 and may also be seen in adults presenting with acute neuroinflammation (4-15%). 3,5-7 Twenty-five per cent to almost 75% will continue to have high titers of MOG antibodies after presenting acutely, 8 with considerable risk of relapse. 9 In one adult-based cohort of 252 patients in the UK with elevated MOG antibodies, 36% had relapses within a median duration of 16 months. 8 Steroids, intravenous immunoglobulin (IVIG), and plasma exchange 10 may be beneficial in reducing symptomatology at the time of an acute event, but are unlikely to decrease the risk of relapse.There is variable support in the literature for the relevance of persistent MOG antibody status for predicting recurrent disease. 11,12 However, prevention of recurrence in the face of repeated neuroinflammatory events prevent future disability. Given the potential for irreversible neurological disability, 13 and the robust response of other antibody-mediated conditions to B-cell suppression with rituximab therapy, 14 we used a standardized treatment protocol using rituximab in children with recurrent central nervous system (CNS) inflammatory disease and persistent MOG antibody positivity 12 weeks or more af...

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

“…Its use has also been described in relation to all subtypes of MOG-IgG related disease in children. In a recently published study, no new MRI lesions or clinical relapses were observed in 10/12 children with a relapsing MOG-IgG associated disorder while B-cells were suppressed on rituximab treatment, and 4/6 children had clinical relapses occurring in the context of B-cell repopulation ( 77 ). Another retrospective series reported a decrease in ARR in MOG-IgG positive children, from 2.12 to 0.67 ( n = 9) while using rituximab ( 78 ).…”

“…Thus, it is justifiable to consider initiation of preventive therapies in children showing persistent MOG-IgG seropositivity after a first attack or after developing a relapsing disease. Sustained remission during treatment with IVIG and with currently available immunosuppressants such as azathioprine, mycophenolate mofetil, or rituximab has been reported but the optimal drug and duration of therapy is not yet clear ( 77 , 78 , 95 , 120 ).…”

Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study

“…Conventional immunosuppressive therapies have demonstrated clinical benefits for reducing relapses [ 6 ], but biologic agents have been rarely used. Thus, rituximab (RTX), an anti-CD20 monoclonal antibody, tocilizumab (TCZ), an IL-6 monoclonal antibody [ 12 , 19 , 20 , 21 , 22 ], and anti-TNFα therapy, especially adalimumab (ADA) and infliximab (IFX), have been only used in some refractory cases [ 23 , 24 , 25 , 26 , 27 ].…”

Myelin oligodendrocyte glycoprotein antibodies associated disease: how important are B cells?

“…Albassam et al. 's report adds to a subgroup of patients with MOG‐Ab associated diseases who relapsed on rituximab despite B cell depletion, suggesting that the pathobiology of the disease may be different in these patients . Alternatively, treatment failure might be explained by antibody‐producing cells in the central nervous system, despite peripheral B cell depletion.…”

“…Albassam et al 3 report 12 children with MOG-Ab associated diseases treated with rituximab. These children were part of a larger cohort of 39 children with MOG-Ab presenting over the study period of which only 16 relapsed and remained persistently MOG-Ab positive at 12 weeks from onset.…”