Neuroimmunology Group (M. Nosadini, S.S.M., S.R., F.B., R.C.D.), Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, University of Sydney, Australia; Paediatric Neurology Unit (M. Nosadini), Department of Paediatrics, University of Padua, Italy; Clinical Neuroimmunology Program (G.A.), Division of Child Neurology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, PA; Neurology Department (C.J.R.), Lady Cilento Children's Hospital, University of Queensland, Australia; Pediatric Multiple Sclerosis and Related Diseases Program (L.A.B., M.P.G.), Boston Children's Hospital, Boston, MA; Department of Neurology (S.R.), Westmead Hospital, Sydney, Australia; Neurology Department (M. Nolan), Starship Children's Health, Auckland, New Zealand; The Roald Dahl EEG Unit (R.A.), Pediatric Neurosciences Foundation, Alder Hey Children's Hospital, Liverpool, UK; Department of Neurology (R.J.L.), Murdoch Childrens Research Institute and University of Melbourne Department of Paediatrics (R.J.L.), Royal Children's Hospital, Melbourne, Victoria, Australia; Assistance Publique-Hopitaux de Paris (K.D.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children (K.D.), Pediatric Neurology Department, and Université Paris-Sud (K.D.), Inserm U1012, Le Kremlin-Bicêtre, France; and Children's Hospital of Philadelphia (A.T.W., B.B.), University of Pennsylvania, Philadelphia.
Neurol Neuroimmunol Neuroinflamm. 2016 Jan 21;3(1):e188. doi: 10.1212/NXI.0000000000000188. eCollection 2016 Feb.
To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing.
Multicenter retrospective study of 16 children with NMO/NMOSD receiving ≥2 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 ≥10 × 10(6) cells/L).
The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 × 10(6) cells/L, 10 had inadequate monitoring (≤1 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection.
Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further.
This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses.
研究利妥昔单抗在儿科视神经脊髓炎（NMO）/NMO 谱系障碍（NMOSD）中的作用，以及利妥昔单抗、B 细胞再增殖与复发之间的关系，以期改进利妥昔单抗的监测和再给药方案。
对 16 例接受了≥2 个利妥昔单抗疗程的 NMO/NMOSD 患儿进行多中心回顾性研究。根据 CD19 计数，将利妥昔单抗治疗期间的事件分为“再增殖”、“耗竭”或“耗竭失败”复发（再增殖阈值 CD19≥10×10(6)个细胞/L）。
16 例患儿（14 例女性；平均年龄 9.6 岁，范围 1.8-15.3 岁）平均随访 6.1 年（范围 1.6-13.6 年），平均发生 6.1 次事件（范围 1-11 次），共接受了 76 个利妥昔单抗疗程（平均 4.7 个，范围 2-9 个）。在利妥昔单抗治疗前，62.5%的患儿曾接受过硫唑嘌呤、霉酚酸酯或环磷酰胺治疗。从利妥昔单抗到最后一次有记录的 B 细胞耗竭和首次再增殖的中位时间分别为 4.5 个月和 6.8 个月，个体间差异较大。最早的再增殖发生在最低剂量时。与利妥昔单抗治疗前相比，患儿的年化复发率（ARR）显著降低（p=0.003）。在利妥昔单抗治疗期间，有 6 例患儿无复发，但 10 例患儿中有 21 例复发，包括 13 例“再增殖”、3 例“耗竭”和 4 例“耗竭失败”复发。在 13 例“再增殖”复发中，4 例 CD19 为 10-50×10(6)个细胞/L，10 例患儿监测不足（复发前 4 个月内≤1 次 CD19 检测），5 例在检测到再增殖后延迟了再次给药。
利妥昔单抗可有效预防复发，但 B 细胞再增殖会增加复发风险。在 B 细胞再增殖前再次给药可能会进一步降低复发风险。
本研究提供了 IV 级证据，表明利妥昔单抗可显著降低儿科 NMO/NMOSD 的 ARR。本研究还证实了 B 细胞再增殖与复发之间存在关联。
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