Cerqueira João J, Berthele Achim, Cree Bruce A C, Filippi Massimo, Pardo Gabriel, Pearson Owen R, Traboulsee Anthony, Ziemssen Tjalf, Vollmer Timothy, Bernasconi Corrado, Mandel Corey R, Kulyk Inessa, Chognot Cathy, Raposo Catarina, Schneble Hans-Martin, Thanei Gian-Andrea, Incera Elodie, Havrdová Eva K
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
Department of Neurology, School of Medicine, Technical University of Munich, Germany.
Neurology. 2025 Feb 25;104(4):e210142. doi: 10.1212/WNL.0000000000210142. Epub 2025 Jan 30.
Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).
Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period.
Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52-4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94-3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later ( = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time.
A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar to the OCR-OCR group, but disability and brain volume loss accrued during interferon treatment were not recovered. Possible study limitations include assessment bias due to unmaintained blinding during the OLE. These data support OCR as first-line therapy for these patients.
This study provides Class II evidence that OCR delays disease progression in treatment-naïve patients with early-stage RMS.
对于多发性硬化症（MS）患者，若从疾病初发时就开始采用高效疾病修正疗法（DMT）进行治疗，可能会实现更好的疾病控制。本亚组分析评估了高效DMT奥瑞珠单抗（OCR）作为早期复发型MS（RMS）一线治疗的长期疗效和安全性。
在多中心OPERA I/II（NCT01247324/NCT01412333）研究中，对一组初治RMS患者进行了疗效和安全性的事后探索性分析，这些患者接受了≥1剂OCR治疗。患者被随机分为OCR组或干扰素β-1a组，为期96周（双盲对照治疗期[DBP]），之后在开放标签扩展期（OLE）改用OCR治疗。疗效评估包括无疾病活动证据（NEDA-3）、24周确认的残疾进展（CDP）、MRI病变活动、全脑体积变化；安全性结果在9年治疗期内进行评估。
总体而言，纳入了757例患者（干扰素治疗组n = 382，平均年龄36.3岁，65.7%为女性；OCR治疗组n = 375，平均年龄35.5岁，64.0%为女性）；757例中的505例（66.7%）完成了9年的随访。在DBP期间，OCR治疗组和干扰素治疗组患者之间的NEDA状态差异（分别为72.5%和43.8%，优势比3.48，95%CI 2.52 - 4.81）在7年的OLE期间得以维持（48.2%对25.7%；优势比2.72，95%CI 1.94 - 3.82）。9年中，78.7%的OCR治疗患者未观察到24周CDP。在整个研究期间，较晚开始使用OCR的患者脑体积损失在数值上仍然更高（在第336周OLE时为0.09）。在DBP期间，两组的安全性概况相似；在OLE期间未观察到新的安全信号。在连续使用OCR治疗超过9年的时间里，感染率随时间保持较低且稳定。
在DBP期间，与干扰素治疗组患者相比，接受OCR治疗的患者中有更高比例达到了NEDA状态，这在整个OLE期间得以维持。改用OCR后，干扰素治疗组患者的残疾累积和脑体积损失与OCR - OCR组相似，但在干扰素治疗期间累积的残疾和脑体积损失并未恢复。可能的研究局限性包括由于在OLE期间未保持盲法而导致的评估偏倚。这些数据支持将OCR作为这些患者的一线治疗。
本研究提供了II类证据，表明OCR可延缓初治早期RMS患者的疾病进展。
