Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease

Abstract

Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease. Methods This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment. Results Median age at onset was 34.1 years (range 18.0–67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1–89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20–0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine ( n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF ( n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab ( n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab. Conclusion In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD. Electronic supplementary material The online version of this article (10.1186/s12974-019-1525-1) contains supplementary material, which is available to authorized users.

An international multicenter examination of MOG antibody assays

“…There are individuals who fulfill criteria for MS, but are often atypical; perhaps the MOG-IgG result has utility in this context in ruling out MS, and should not be ignored out of hand. Importantly, when extrapolating from experiences on the treatment of NMOSD and a recent larger study on treatment of patients with MOG-IgG from France, disease modifying treatments for MS may not work in MOG-IgG positive patients and may even exacerbate disease 1,[32][33][34] . The third interpretation is that these low positive results that are not reproducible between centers are not useful clinically and in fact dilute the utility of a more specific test.…”

Effects of the Positive Threshold and Data Analysis on Human MOG Antibody Detection by Live Flow Cytometry

“…MOG Ab-associated disorders encompass a disease entity involving the brain, optic nerve, and spinal cord that is distinct from multiple sclerosis (MS) and aquaporin-4 Ab-positive neuromyelitis optica spectrum disorder (NMOSD) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). The reemergence of MOG Ab in the field of autoimmune diagnostics has sparked wide interest, and with ongoing advances in our understanding of MOG Ab-associated disease, requests for MOG Ab testing have risen dramatically, as treatment regimens and prognosis for MOG Ab-positive patients are divergent from MS and aquaporin-4 Ab-positive NMOSD patients (11,16,17). Moreover, some MOG Ab-positive patients, particularly those with relapsing disease or delayed immunotherapy, may accrue residual disability (11,12,(15)(16)(17)(18)(19).…”

“…The reemergence of MOG Ab in the field of autoimmune diagnostics has sparked wide interest, and with ongoing advances in our understanding of MOG Ab-associated disease, requests for MOG Ab testing have risen dramatically, as treatment regimens and prognosis for MOG Ab-positive patients are divergent from MS and aquaporin-4 Ab-positive NMOSD patients (11,16,17). Moreover, some MOG Ab-positive patients, particularly those with relapsing disease or delayed immunotherapy, may accrue residual disability (11,12,(15)(16)(17)(18)(19). As such, early and accurate identification of MOG Ab-seropositivity is crucial.…”

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

“…A study of 197 adults with MOG-Ab observed that titres were higher at relapse than in remission. 4 In a large paediatric study, high MOG-Ab titres (≥1:1280) predicted a recurrent non-multiple sclerosis course with 46% sensitivity and 86% specificity. 5 Overall, patients may remain seropositive for years, despite having a monophasic disease.…”

“…The utility of MOG‐Ab in making treatment decisions remains an area of active debate. A study of 197 adults with MOG‐Ab observed that titres were higher at relapse than in remission . In a large paediatric study, high MOG‐Ab titres (≥1:1280) predicted a recurrent non‐multiple sclerosis course with 46% sensitivity and 86% specificity .…”