From the APHM (L.G.-A., C.B., C.R., M.P., A.R., S.D., F.H., J.P., A.M., B.A.), Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie; Aix-Marseille University (A.R., J.P., A.M., B.A.), CNRS, CRMBM, Marseille; Centre hospitalier d'Ajaccio (P.D.), Service de Neurologie, Ajaccio; APHM (F.V.), Hôpital de la Timone, Service d'immunologie, Marseille Immunopôle; Aix Marseille University (F.V.), CNRS, INSERM, CIML; and APHM (P.B.-P.), Hôpital de la Timone, Service Pharmacie, Marseille, France.
Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200231. doi: 10.1212/NXI.0000000000200231. Epub 2024 Apr 16.
Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher risk associated with fingolimod (FING).
We performed a retrospective analysis of a structured prospective data collection including all consecutive patients with relapsing MS who were prescribed RTX/OCR in the MS center of Marseille. Cox proportional hazards models were applied to clinical and MRI outcomes.
We included 321 patients with a median (interquartile range [IQR]) follow-up of 3.5 years (1.5-5) after RTX/OCR initiation. At the first RTX/OCR infusion, the mean (SD) age of patients was 37 (10) years, and the median (IQR) disease duration was 8 years (3-15): 68 patients did not receive treatment before RTX/OCR and 108 switched from FING, 47 from low efficacy therapy, and 98 from natalizumab. For statistical analysis, the group "FING" was divided into "short-FING" and "long-FING" groups according to the median value of the group's washout period (27 days). On Cox proportional hazards analysis, for only the "long-FING" group, the risk of relapse within the first 6 months of RTX/OCR was increased as compared with patients without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; < 0.01). Previous DMT and washout period duration of FING had no effect on B-cell levels at 6 months. Beyond the first 6 months of RTX/OCR, age <40 years was associated with increased risk of relapse (HR: 3.93; 95% CI 1.30-11.89; = 0.01), male sex with increased risk of new T2 lesions (HR: 2.26; 95% CI 1.08-4.74; = 0.03), and EDSS ≥2 with increased risk of disability accumulation (HR: 3.01; 95% CI 1.34-6.74; < 0.01). Previous DMT had no effect on the effectiveness of RTX/OCR beyond 6 months after initiation.
For patients switching from FING to RTX/OCR, the risk of disease reactivation within the first 6 months of treatment was increased as compared with patients with other DMT or no previous DMT only when the washout period exceeded 26 days. Neither FING nor other previous DMT reduced the effectiveness of RTX/OCR beyond the first 6 months of treatment.
真实世界研究表明，多发性硬化症（MS）患者在转为利妥昔单抗（RTX）或奥瑞珠单抗（OCR）后，疾病活动的风险可能因先前的疾病修正治疗（DMT）而异，与 fingolimod（FING）相比，风险更高。
我们对包括所有在马赛 MS 中心接受 RTX/OCR 治疗的复发性 MS 连续患者的结构化前瞻性数据采集进行了回顾性分析。应用 Cox 比例风险模型评估临床和 MRI 结果。
我们纳入了 321 名患者，在 RTX/OCR 开始后中位（四分位间距 [IQR]）随访 3.5 年（1.5-5）。在首次 RTX/OCR 输注时，患者的平均（SD）年龄为 37（10）岁，中位（IQR）病程为 8 年（3-15）：68 名患者在接受 RTX/OCR 治疗前未接受治疗，108 名患者从 FING 转为 RTX/OCR，47 名患者从低疗效治疗转为 RTX/OCR，98 名患者从那他珠单抗转为 RTX/OCR。为了进行统计分析，根据 FING 洗脱期（27 天）的中位数，将“FING”组分为“短洗脱 FING”和“长洗脱 FING”组。在 Cox 比例风险分析中，仅在“长洗脱 FING”组中，与未接受过先前 DMT 的患者相比，RTX/OCR 治疗的前 6 个月内复发的风险增加（风险比 [HR]：8.78；95%置信区间 [CI]：1.72-44.86；<0.01）。先前的 DMT 和 FING 的洗脱期持续时间对 6 个月时的 B 细胞水平没有影响。在接受 RTX/OCR 治疗的前 6 个月之后，年龄<40 岁与复发风险增加相关（HR：3.93；95%CI：1.30-11.89；=0.01），男性与新 T2 病变风险增加相关（HR：2.26；95%CI：1.08-4.74；=0.03），EDSS≥2 与残疾累积风险增加相关（HR：3.01；95%CI：1.34-6.74；<0.01）。在接受 RTX/OCR 治疗 6 个月后，先前的 DMT 对其疗效没有影响。
对于从 FING 转为 RTX/OCR 的患者，与接受其他 DMT 或未接受任何 DMT 的患者相比，只有当洗脱期超过 26 天时，治疗的前 6 个月内疾病复发的风险才会增加。FING 或其他先前的 DMT 都不会降低 RTX/OCR 治疗 6 个月后的疗效。
