Editors' Note: Evaluation of Efficacy and Tolerability of First-Line Therapies in NMOSD

Abstract

In the article, “Evaluation of Efficacy and Tolerability of First-Line Therapies in NMOSD,” Dr. Poupart et al. compared the efficacy and risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). Among 136 patients, they found that the use of first-line rituximab seemed more effective than mycophenolate mofetil (MMF) in suppressing clinical activity, independent of the antibody status. In response, Dr. Leite notes that rituximab is currently used as second-line therapy in most countries, but because rituximab and MMF have similar tolerability but rituximab had superior efficacy, an argument could be made for considering rituximab as a first-line therapy. In addition to noting that the apparent similarity in efficacy of rituximab and azathioprine was unexpected and contradicts other studies, Dr. Leite raises a couple of concerns about rituximab, including (1) rituximab-associated hypogammaglobulinemia (assessment of which would require analyses of plasma immunoglobulin levels) and (2) potential differences in the role of rituximab for chronic management between NMOSD patients with aquaporin-4 (AQP4) antibodies vs myelin oligodendrocyte (MOG) antibodies, who were analyzed together in this study. Responding to these comments, the authors note the small sample size of the azathioprine group, which limited statistical power. They also report that 22.7% of 44 patients treated with rituximab who had immunoglobulin results available met their definition of hypogammaglobulinemia, with one such patient having a serious infection. They agree that MOG and AQP4 diseases are different processes but note that they chose to focus on the broader NMOSD phenotype because the optimal management of MOG-positive patients is also uncertain. The authors note that there was no significant difference in therapeutic response based on the antibody status. This exchange highlights the need to further examine the commonly used treatment regimens for NMOSD in controlled trials, both in those that are MOG positive and those that harbor AQP4 antibodies. In the article, “Evaluation of Efficacy and Tolerability of First-Line Therapies in NMOSD,” Dr. Poupart et al. compared the efficacy and risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). Among 136 patients, they found that the use of first-line rituximab seemed more effective than mycophenolate mofetil (MMF) in suppressing clinical activity, independent of the antibody status. In response, Dr. Leite notes that rituximab is currently used as second-line therapy in most countries, but because rituximab and MMF have similar tolerability but rituximab had superior efficacy, an argument could be made for considering rituximab as a first-line therapy. In addition to noting that the apparent similarity in efficacy of rituximab and azathioprine was unexpected and contradicts other studies, Dr. Leite raises a couple of concerns about rituximab, including (1) rituximab-associated hypogammaglobulinemia (assessment of which would require analyses of plasma immunoglobulin levels) and (2) potential differences in the role of rituximab for chronic management between NMOSD patients with aquaporin-4 (AQP4) antibodies vs myelin oligodendrocyte (MOG) antibodies, who were analyzed together in this study. Responding to these comments, the authors note the small sample size of the azathioprine group, which limited statistical power. They also report that 22.7% of 44 patients treated with rituximab who had immunoglobulin results available met their definition of hypogammaglobulinemia, with one such patient having a serious infection. They agree that MOG and AQP4 diseases are different processes but note that they chose to focus on the broader NMOSD phenotype because the optimal management of MOG-positive patients is also uncertain. The authors note that there was no significant difference in therapeutic response based on the antibody status. This exchange highlights the need to further examine the commonly used treatment regimens for NMOSD in controlled trials, both in those that are MOG positive and those that harbor AQP4 antibodies.