To explore whether time to diagnosis, time to treatment initiation, and age to reach disability milestones have changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS) diagnostic criteria periods.

This retrospective study was based on data collected prospectively from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into 5 periods according to different MS criteria, and the times to MS diagnosis and treatment initiation were evaluated. The age at which patients with MS reached an Expanded Disability Status Scale (EDSS) score ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Last, to remove the classic Will Rogers phenomenon by which the use of different MS criteria over time might result in a changes of prognosis, the 2017 McDonald criteria were applied, and age at EDSS score ≥3.0 was assessed by Cox regression.

In total, 1,174 patients were included. The median time from CIS to MS diagnosis and from CIS to treatment initiation showed a 77% and 82% reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching an EDSS score ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24–0.90) for McDonald 2001, aHR 0.25 (0.12–0.54) for McDonald 2005, aHR 0.30 (0.12–0.75) for McDonald 2010, and aHR 0.07 (0.01–0.45) for McDonald 2017. Patients in the early-treatment group displayed an aHR of 0.53 (0.33–0.85) of reaching age at EDSS score ≥3.0 compared to those in the late-treatment group. Changes in prognosis together with early-treatment effect were maintained after the exclusion of possible bias derived from the use of different diagnostic criteria over time (Will Rogers phenomenon).

A continuous decrease in the time to MS diagnosis and treatment initiation was observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. The prognostic improvement is maintained after the Will Rogers phenomenon is discarded, and early treatment appears to be the most likely contributing factor.

根据不同的多发性硬化症 (MS) 诊断标准时期，探讨临床孤立综合征 (CIS) 患者的诊断时间、开始治疗的时间和达到残疾里程碑的年龄是否发生了变化。

这项回顾性研究基于 1994 年至 2020 年间从巴塞罗那-独联体队列前瞻性收集的数据。根据不同的 MS 标准将患者分为 5 个时期，并评估 MS 诊断和治疗开始的时间。根据诊断标准时期，通过 Cox 回归分析评估 MS 患者达到扩展残疾状态量表 (EDSS) 评分≥3.0 的年龄。最后，为了消除经典的 Will Rogers 现象，即随着时间的推移使用不同的 MS 标准可能导致预后发生变化，应用了 2017 McDonald 标准，并通过 Cox 回归评估了 EDSS 评分≥3.0 的年龄。

总共包括 1,174 名患者。从 CIS 到 MS 诊断以及从 CIS 到治疗开始的中位时间显示，从 Poser 到 McDonald 2017 诊断标准期分别减少了 77% 和 82%。与在较早诊断期（参考类别 Poser 期）诊断出的同龄患者相比，在最近诊断标准期诊断出的特定年龄患者达到 EDSS 评分≥3.0 的风险更低：调整后的风险比 (aHR) 0.47 (95 McDonald 2001 的置信区间为 0.24–0.90)，McDonald 2005 的 aHR 为 0.25 (0.12–0.54)，McDonald 2010 的 aHR 为 0.30 (0.12–0.75)，McDonald 早期患者的 aHR 为 0.07 (0.01–0.45)。与晚期治疗组相比，治疗组在 EDSS 评分≥3.0 时的年龄 aHR 为 0.53 (0.33–0.85)。

在整个诊断标准期间，观察到 MS 诊断和治疗开始的时间持续减少。总体而言，在最近的诊断标准期间诊断出的患者显示出较低的残疾风险。排除威尔罗杰斯现象后，预后改善得以维持，早期治疗似乎是最可能的促成因素。