From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.
Neurology. 2020 Apr 14;94(15):e1645-e1656. doi: 10.1212/WNL.0000000000009245. Epub 2020 Mar 13.
To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD).
We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR).
A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF ( = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA.
The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status.
That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.
比较在视神经脊髓炎谱系疾病（NMOSD）患者中，早期作为一线治疗使用的免疫抑制剂的疗效和严重感染事件风险。
我们回顾性纳入了 NMOSD 患者，这些患者在发病后 3 年内开始使用一线免疫抑制剂，且 aquaporin 4 或髓鞘少突胶质细胞糖蛋白抗体呈阳性。主要结局为开始使用免疫抑制剂后复发的发生；次要结局为年复发率（ARR）。
共纳入 136 例患者：62 例（45.6%）接受利妥昔单抗（RTX）治疗，42 例（30.9%）接受霉酚酸酯（MMF）治疗，23 例（16.9%）接受硫唑嘌呤（AZA）治疗。在校正发病年龄、性别、抗体状态、疾病持续时间、治疗前 ARR、皮质类固醇摄入和复发部位后，与 RTX 治疗组相比，MMF 治疗组的复发风险更高（风险比[HR]，2.74[1.17-6.40]；=0.020）。我们未观察到 RTX 治疗组和 AZA 治疗组之间存在差异（HR，2.13[0.72-6.28]；=0.17）。未发现抗体状态和免疫抑制剂治疗之间存在交互作用。RTX 组的 ARR 低于 MMF 组（=0.039），但与 AZA 组无差异。我们观察到 9 例严重感染事件发生于 MMF 组，6 例发生于 RTX 组，而 AZA 组无此事件。
与 MMF 相比，NMOSD 一线应用 RTX 似乎能更有效地抑制临床活动，且与抗体状态无关。
该研究提供了 III 级证据，表明对于 NMOSD 患者，一线 RTX 优于 MMF，可降低复发风险。
