Contributions
Abstract: 104
Type: Oral
Therapeutic evidence in neuromyelitis optica (NMO) has been based on non-randomized, non-placebo-controlled retrospective studies of patients treated with candidate disease-modifying drugs, and thus the evidence levels were low. This is mainly because NMO, if untreated, carries a poor prognosis and many neurologists treating NMO patients thought placebo-controlled trials in NMO would not be justified. However, clinical trial designs in NMO have been a matter of active debate (Weinshenker et al. Neurology 2015), and by introducing time-to-attack primary outcome, limited duration of potential placebo exposure, unequal randomization, unblinded data safety monitoring board and interim futility analysis, a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity were proposed and approved by drug regulatory authorities (Cree et al. Mult Scler 2015). Add-on trials are also ongoing.
A variety of immunosuppressive drugs are administered in NMO. Relatively non-specific immunosuppressants (prednisolone, azathioprine, mycophenolate mofetil, methotrexate, mitoxantrone, tacrolimus, etc) have been widely used, but in recent years, monoclonal antibodies targeting specific immune molecules (rituximab, tocilizumab, eculizumab, anti-CD19, etc) have also been administered in clinical practice or are being studied in clinical trials. Treatment algorithm of NMO depends on approval, availability, neurologist"s threpeutic experience, cost, patient preferences etc. Meanwhile, of particular note is that some disease modifying drugs for multiple sclerosis (MS) (interferon-beta, natalizumab, and fingolimod) can aggravate aquaporin 4 (AQP4)-IgG-positive NMO.
Management of AQP4-IgG-seronegative NMO including myelin oligodendrocyte glycoprotein (MOG)-IgG-positive NMO has not been established. But generally, compared to AQP4-IgG-positive disease, plasma exchange is not so often needed as a rescue therapy of acute exacerbation. Some patients with this type of disease may have monophasic disease, but in relapsing disease, immunosuppressive drugs are often administered. Such MS drugs as interferon-beta and fingolimod appear not to be efficacious in MOG-IgG-positive NMO although available data is limited.
Disclosure: Kazuo Fujihara serves on scientific advisory boards for Bayer Schering, Biogen Idec, Mitsubishi Tanabe Pharma, Novartis, Chugai, Ono, Nihon Pharmaceutical, Merck Serono, Alexion, and Medimmune; has received funding for travel and speaker honoraria from Bayer Schering, Biogen Idec, Eisai, Mitsubishi Tanabe Pharma, Novartis, Astellas, Takeda, Asahi Kasei Medical, Daiichi Sankyo, and Nihon Pharmaceutical; has received research support from Bayer Schering, Biogen Idec, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva, Mitsubishi Tanabe, Teijin, Chugai, Ono, Nihon Pharmaceutical, and Genzyme Japan; is funded by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Welfare and Labor of Japan.
Abstract: 104
Type: Oral
Therapeutic evidence in neuromyelitis optica (NMO) has been based on non-randomized, non-placebo-controlled retrospective studies of patients treated with candidate disease-modifying drugs, and thus the evidence levels were low. This is mainly because NMO, if untreated, carries a poor prognosis and many neurologists treating NMO patients thought placebo-controlled trials in NMO would not be justified. However, clinical trial designs in NMO have been a matter of active debate (Weinshenker et al. Neurology 2015), and by introducing time-to-attack primary outcome, limited duration of potential placebo exposure, unequal randomization, unblinded data safety monitoring board and interim futility analysis, a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity were proposed and approved by drug regulatory authorities (Cree et al. Mult Scler 2015). Add-on trials are also ongoing.
A variety of immunosuppressive drugs are administered in NMO. Relatively non-specific immunosuppressants (prednisolone, azathioprine, mycophenolate mofetil, methotrexate, mitoxantrone, tacrolimus, etc) have been widely used, but in recent years, monoclonal antibodies targeting specific immune molecules (rituximab, tocilizumab, eculizumab, anti-CD19, etc) have also been administered in clinical practice or are being studied in clinical trials. Treatment algorithm of NMO depends on approval, availability, neurologist"s threpeutic experience, cost, patient preferences etc. Meanwhile, of particular note is that some disease modifying drugs for multiple sclerosis (MS) (interferon-beta, natalizumab, and fingolimod) can aggravate aquaporin 4 (AQP4)-IgG-positive NMO.
Management of AQP4-IgG-seronegative NMO including myelin oligodendrocyte glycoprotein (MOG)-IgG-positive NMO has not been established. But generally, compared to AQP4-IgG-positive disease, plasma exchange is not so often needed as a rescue therapy of acute exacerbation. Some patients with this type of disease may have monophasic disease, but in relapsing disease, immunosuppressive drugs are often administered. Such MS drugs as interferon-beta and fingolimod appear not to be efficacious in MOG-IgG-positive NMO although available data is limited.
Disclosure: Kazuo Fujihara serves on scientific advisory boards for Bayer Schering, Biogen Idec, Mitsubishi Tanabe Pharma, Novartis, Chugai, Ono, Nihon Pharmaceutical, Merck Serono, Alexion, and Medimmune; has received funding for travel and speaker honoraria from Bayer Schering, Biogen Idec, Eisai, Mitsubishi Tanabe Pharma, Novartis, Astellas, Takeda, Asahi Kasei Medical, Daiichi Sankyo, and Nihon Pharmaceutical; has received research support from Bayer Schering, Biogen Idec, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva, Mitsubishi Tanabe, Teijin, Chugai, Ono, Nihon Pharmaceutical, and Genzyme Japan; is funded by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Welfare and Labor of Japan.