Cao Shugang, Wang Xiaoyuan, Ji Xiaopei, Tian Jingluan, Zhu Yunfei, Wang Xin, Gu Yanzheng, Duan Xiaoyu, Xiao Xinyi, Fang Qi, Zhang Xueguang, Xue Qun
Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Neurology, Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei 230011, China.
Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Mult Scler Relat Disord. 2023 Feb;70:104524. doi: 10.1016/j.msard.2023.104524. Epub 2023 Jan 16.
To explore the B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab (mRTX) regimen for neuromyelitis optica spectrum disorder (NMOSD).
NMOSD patients treated with mRTX were recruited, and the percentages of total CD19 B cells and CD27 memory B cells were dynamically detected by flow cytometry. The annualized relapse rate (ARR) and expanded disability status scale (EDSS) scores were compared before and after mRTX treatment, and the differences in B-cell values were compared between groups.
A total of 34 patients with NMOSD were ultimately enrolled. The EDSS score decreased from 2.5 (1.5, 3.0) to 1.3 (1.0, 2.0), and the ARR decreased from 1.0 (0, 2.0) to 0 (0, 0) (p < 0.001). Relapses occurred in 6 patients, with total CD19 B-cell percentages of 3.25% (2.7%, 3.7%) and CD27 memory B-cell percentages of 0.3% (0.2%, 0.3%) at initial relapse. Twenty-eight patients (82.4%) remained relapse-free with 84 doses of mRTX. Before 56 repeated doses, the total CD19 B cells and CD27 memory B cells were 4.00% (3.14%, 5.32%) and 0.26% (0.17%, 0.40%), respectively. The mean dosing interval was 9.2 months. Both total CD19 B cells and CD27 memory B cells proliferated over time after mRTX use, with significantly faster proliferation rates in the later stages. In 28 relapse-free patients, the mean time to reach 1% for total CD19 B cells was 210 days, and the mean time to reach 3% was 240 days, with the mean interval from 1% to 3% of 65 days. Twenty-five relapse-free patients had no significant differences in maximum, minimum, and mean B-cell values compared to those of 6 patients with relapse.
The high rate of B-cell proliferation under the mRTX regimen indicates that closer dynamic B-cell monitoring is required to guide repeated mRTX dosing. Sustained depletion of total CD19 B cells targeting < 3% of lymphocytes may be feasible, enabling extended dosing intervals.
探讨改良低剂量利妥昔单抗（mRTX）方案治疗视神经脊髓炎谱系障碍（NMOSD）时B细胞增殖特征及监测意义。
招募接受mRTX治疗的NMOSD患者，采用流式细胞术动态检测总CD19 B细胞和CD27记忆B细胞百分比。比较mRTX治疗前后的年化复发率（ARR）和扩展残疾状态量表（EDSS）评分，并比较组间B细胞值的差异。
最终纳入34例NMOSD患者。EDSS评分从2.5（1.5，3.0）降至1.3（1.0，2.0），ARR从1.0（0，2.0）降至0（0，0）（p<0.001）。6例患者复发，初次复发时总CD19 B细胞百分比为3.25%（2.7%，3.7%），CD27记忆B细胞百分比为0.3%（0.2%，0.3%）。28例（82.4%）患者接受84剂mRTX后无复发。在56次重复给药前，总CD19 B细胞和CD27记忆B细胞分别为4.00%（3.14%，5.32%）和0.26%（0.17%，0.40%）。平均给药间隔为9.2个月。使用mRTX后，总CD19 B细胞和CD27记忆B细胞均随时间增殖，后期增殖速度明显加快。在28例无复发患者中，总CD19 B细胞达到1%的平均时间为210天，达到3%的平均时间为240天，从1%到3%的平均间隔为65天。25例无复发患者与6例复发患者相比，B细胞最大值、最小值和平均值无显著差异。
mRTX方案下B细胞增殖率高，表明需要更密切的动态B细胞监测以指导mRTX重复给药。以淋巴细胞的<3%为靶点持续消耗总CD19 B细胞可能是可行的，可延长给药间隔。
