Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, University of Florence, Florence, Italy.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro Policlinico, Bari, Italy.
JAMA Neurol. 2022 Sep 1;79(9):869-878. doi: 10.1001/jamaneurol.2022.1929.
Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking.
To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS.
DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up.
The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models.
Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective).
From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P < .001), superimposed relapses (aHR, 2.37; 95% CI, 1.24-4.54; P = .009), and DMT exposure (aHR, 1.75; 95% CI, 1.04-2.94; P = .03) were associated with a higher risk of an EDSS score of 7.0, whereas the interaction term between DMT and superimposed relapses was associated with a reduced risk of EDSS score of 7.0 (aHR, 0.33; 95% CI, 0.16-0.71; P = .004). Similar findings were obtained when treatment according to DMT class was considered and when DMT was included as a time-dependent covariate. These results were confirmed in the subgroup of patients with available magnetic resonance imaging data.
Results of this comparative effectiveness research study suggest that inflammation also occurs in patients with PPMS, may contribute to long-term disability, and may be associated with a reduced risk of becoming wheelchair dependent by current licensed DMTs.
除了奥瑞珠单抗，原发性进行性多发性硬化症（PPMS）的治疗选择有限。
在 PPMS 患者的真实世界人群中，研究 DMT 对成为轮椅依赖风险的影响。
设计、地点和参与者：这是一项多中心、观察性、回顾性、比较有效性研究。于 2018 年 11 月 28 日从意大利多发性硬化症登记处提取数据，并于 2021 年 6 月至 12 月进行分析。平均研究随访时间为 11 年。研究队列包括至少有 3 年扩展残疾状况量表（EDSS）评估和 3 年随访时间的 PPMS 诊断患者。
通过多变量 Cox 回归模型评估达到 EDSS 评分 7.0 的风险。
在结果发生之前接受 DMT 的患者被认为是治疗过的。DMT 被评估为一个时间依赖性变量，并根据 DMT 类别（中度和高度有效）进行评估。
在总共 3298 名 PPMS 患者中，有 2633 名因未满足评估奥瑞珠单抗在成人 PPMS 中的疗效和安全性的多中心、随机、平行组、双盲、安慰剂对照 III 期研究（ORATORIO 试验）的纳入标准而被排除在外。在其余 665 名患者（平均[标准差]年龄 43.0[10.7]岁；366 名女性患者[55.0%]）中，有 409 名进一步被选择进行倾向评分匹配（288 名治疗组和 121 名未治疗组）。在匹配队列中，在研究随访期间，409 名患者中有 37%（152 名）在平均（标准差）随访 10.6（5.6）年后达到 EDSS 评分 7.0。基线时更高的 EDSS 评分（调整后的危险比[aHR]，1.32；95%置信区间[CI]，1.13-1.55；P<.001）、叠加复发（aHR，2.37；95%CI，1.24-4.54；P=0.009）和 DMT 暴露（aHR，1.75；95%CI，1.04-2.94；P=0.03）与更高的 EDSS 评分 7.0 风险相关，而 DMT 和叠加复发之间的交互项与 EDSS 评分 7.0 的风险降低相关（aHR，0.33；95%CI，0.16-0.71；P=0.004）。当考虑 DMT 类别进行治疗时，以及当 DMT 被视为时间依赖性协变量时，也得到了类似的发现。这些结果在有磁共振成像数据的患者亚组中得到了证实。
这项比较有效性研究的结果表明，炎症也发生在 PPMS 患者中，可能导致长期残疾，并可能与当前许可的 DMT 降低成为轮椅依赖的风险有关。
