无病活动状态、缓解、残疾进展和脑损伤 (NEDA-3) 在多发性硬化长期结局中的预后准确性。
Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis.
机构信息
From the Department of Neurosciences (L.P., S.H., C.T., C.G.), S. Camillo-Forlanini Hospital; Department of Human Neurosciences (S.R., C.P.), Sapienza University; and Neuroimmunology Unit (S.R.), Santa Lucia Foundation, Rome, Italy.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2021 Aug 9;8(6). doi: 10.1212/NXI.0000000000001059. Print 2021 Nov.
BACKGROUND AND OBJECTIVES
To estimate the proportions of patients with relapsing-remitting multiple sclerosis who despite achieving the no evidence of disease activity-3 (NEDA-3) status in the first 2 treatment years experienced relapse-associated worsening (RAW) or progression independent from relapse activity (PIRA) in the following years.
METHODS
We selected patients with NEDA-3-defined as no relapse, no disability worsening, and no MRI activity-in the first 2 years of either glatiramer acetate or interferon beta as initial treatment. We estimated the long-term probability of subsequent RAW and PIRA (considered as 2 contrasting outcomes) by cumulative incidence functions. Competing risk regressions were used to identify the baseline (i.e., at treatment start) predictors of RAW and PIRA.
RESULTS
Of 687 patients, 224 (32.6%) had NEDA-3 in the first 2 treatment years. After a median follow-up time of 12 years from treatment start, 58 patients (26%) experienced disability accrual: 31 (14%) had RAW and 27 (12%) had PIRA. RAW was predicted by the presence of >9 T2 lesions (subdistribution hazard ratio [SHR] = 3.92, = 0.012) and contrast-enhancing lesions (SHR = 2.38, = 0.047) on baseline MRI scan and either temporary or permanent discontinuation of the initial treatment (SHR = 1.11, = 0.015). PIRA was predicted by advancing age (SHR = 1.05, = 0.036 for each year increase) and presence of ≥1 spinal cord lesion on baseline MRI scan (SHR = 4.08, = 0.016).
DISCUSSION
The adoption of NEDA-3 criteria led to prognostic misclassification in 1 of 4 patients. Different risk factors were associated with RAW and PIRA, suggesting alternative mechanisms for disability accrual.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that in patients with RRMS who attained NEDA-3 status, subsequent RAW was associated with baseline MRI activity and discontinuation of treatment and PIRA was associated with age and the presence of baseline spinal cord lesions.
背景和目的
评估在最初 2 年的治疗中达到无疾病活动-3（NEDA-3）状态的复发性缓解型多发性硬化症（RRMS）患者，在随后的年份中是否出现与复发相关的恶化（RAW）或与复发无关的进展（PIRA）。
方法
我们选择了在最初 2 年内使用醋酸格拉替雷或干扰素β作为初始治疗的患者，这些患者符合 NEDA-3 定义，即无复发、无残疾恶化和无 MRI 活动。我们通过累积发病率函数估计随后发生 RAW 和 PIRA（视为 2 种对比结局）的长期概率。使用竞争风险回归来确定 RAW 和 PIRA 的基线（即治疗开始时）预测因素。
结果
在 687 名患者中，有 224 名（32.6%）在最初 2 年的治疗中达到了 NEDA-3。从治疗开始后中位随访 12 年，有 58 名患者（26%）出现了残疾进展：31 名（14%）发生了 RAW，27 名（12%）发生了 PIRA。RAW 由基线 MRI 扫描上存在>9 个 T2 病变（亚分布危险比 [SHR] = 3.92， = 0.012）和对比增强病变（SHR = 2.38， = 0.047）、初始治疗的暂时或永久性停药（SHR = 1.11， = 0.015）预测。PIRA 由年龄增加（每增加 1 岁，SHR = 1.05， = 0.036）和基线 MRI 扫描上存在≥1 个脊髓病变（SHR = 4.08， = 0.016）预测。
讨论
采用 NEDA-3 标准导致 1/4 的患者出现预后误分类。RAW 和 PIRA 与不同的危险因素相关，提示残疾进展的机制不同。
证据分类
本研究提供了 II 级证据，表明在达到 NEDA-3 状态的 RRMS 患者中，随后的 RAW 与基线 MRI 活动和治疗停药有关，而 PIRA 与年龄和基线脊髓病变有关。
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