Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia, " University of Catania, Via S. Sofia 78, 95100, Catania, Italy.
Multiple Sclerosis Center, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.
Neurotherapeutics. 2023 Oct;20(6):1696-1706. doi: 10.1007/s13311-023-01415-y. Epub 2023 Aug 23.
Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07-3.65; p = 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.
奥瑞珠单抗是一种针对表达 CD20 的 B 细胞的人源化单克隆抗体。在招募年龄<55 岁且最大扩展残疾状态量表（EDSS）评分<6.5 的患者的 3 期临床试验中，评估了奥瑞珠单抗对原发性进展型多发性硬化症（PPMS）的作用。然而，对于年龄较大、残疾程度较高且疾病持续时间较长的患者，我们知之甚少。我们旨在评估奥瑞珠单抗在超出 ORATORIO 入选标准的 PPMS 患者中的临床疗效。这项多中心回顾性研究收集了意大利多发性硬化症登记处中参与研究的意大利多发性硬化症中心的患者接受奥瑞珠单抗治疗的数据，这些患者在 2017 年 5 月至 2022 年 6 月期间接受治疗，并符合同情用药项目的要求。计算确认的扩展残疾状态量表恶化（CEW）（定义为 EDSS 评分从基线至少增加 1 分或至少增加 2 分，且在 T12 和 T24 时得到确认）。在数据提取时，在接受奥瑞珠单抗治疗的 887 例 PPMS 患者中，有 589 例（平均年龄 49.7±10.7 岁，242 例[41.1%]为女性）符合纳入标准。平均随访时间为 41.3±12.3 个月。共有 149 例（25.3%）患者根据 ORATORIO 标准（ORATORIO 组）接受奥瑞珠单抗治疗，440 例（74.7%）患者不符合 ORATORIO 标准（非 ORATORIO 组）。在 ORATORIO 和非 ORATORIO 组中，12 个月和 24 个月 CEW≤1 分的累积概率无差异。Cox 回归分析显示，年龄>65 岁（HR 2.51，25%CI 1.07-3.65；p=0.01）与 24 个月时 CEW 风险增加相关。不符合 ORATORIO 报销标准的患者可能从奥瑞珠单抗治疗中获益，因为疾病活动度、疾病持续时间和 EDSS 似乎不影响残疾结局。我们的结果表明，对于年龄在 65 岁以下的患者，可能需要扩大这种强效药物的使用范围。
