MS Centre, Department of Neurosciences, San Camillo Forlanini Hospital, Rome, Italy.
Mult Scler. 2024 Sep;30(10):1309-1321. doi: 10.1177/13524585241266180. Epub 2024 Jul 31.
To summarize the current evidence on relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) through a quantitative synthesis of real-world studies.
Scientific databases were searched to identify suitable articles. Random-effects meta-analyses, subgroup analyses and meta-regression models were ran to provide pooled estimates of RAW and PIRA events and to identify their potential moderators (PROSPERO registration: CRD42024503895).
Eighteen articles met the eligibility criteria, with a pooled sample size of 52,667 patients (93% relapsing-remitting, 6% clinically isolated syndrome and 1% progressive) followed for 2.4 to 12.1 years, yielding to 415,825 patient-years. Pooled event rates for RAW and PIRA were 1.6 (95 confidence interval (CI) = 1.1-2.1) and 3.1 (95% CI = 2.3-3.9) per 100 patient-years, respectively. Less RAW events were found in cohorts including patients with progressive course (β = -0.069, = 0.006) and under high-efficacy disease-modifying treatments (DMTs) (β = -0.031, = 0.007), while PIRA events were directly related to older age (β = 0.397, = 0.027). In addition, we found significant differences in PIRA event rates according to the criteria adopted to define confirmed disability accrual ( < 0.05).
PIRA accounts for most events causing disability accumulation in the real-world setting, even at the earlier disease stages, whereas RAW represents a less frequent phenomenon, likely due to effective treatments. The detection and statistical analysis of PIRA outcomes pose challenges, raising the risk of erroneous inference. When interpreting our findings, caution is needed given the wide heterogeneity of included studies.
通过对真实世界研究进行定量综合，总结与复发相关的恶化（RAW）和与复发无关的进展（PIRA）的现有证据。
检索科学数据库以确定合适的文章。进行随机效应荟萃分析、亚组分析和荟萃回归模型分析，以提供 RAW 和 PIRA 事件的汇总估计，并确定其潜在的调节因素（PROSPERO 注册：CRD42024503895）。
18 篇文章符合入选标准，共有 52667 例患者（93%为复发缓解型，6%为临床孤立综合征，1%为进展型）接受了 2.4 至 12.1 年的随访，共产生 415825 患者年。RAW 和 PIRA 的汇总事件发生率分别为 1.6（95%置信区间（CI）=1.1-2.1）和 3.1（95%CI=2.3-3.9）/100 患者年。在包括进展性病程（β=-0.069， =0.006）和高效疾病修正治疗（DMT）（β=-0.031， =0.007）的队列中，RAW 事件较少，而 PIRA 事件与年龄较大呈直接相关（β=0.397， =0.027）。此外，我们发现根据采用的定义确诊残疾累积的标准，PIRA 事件发生率存在显著差异（ < 0.05）。
在真实世界环境中，PIRA 导致残疾累积的大多数事件，即使在疾病早期阶段也是如此，而 RAW 是一种不太常见的现象，可能是由于有效治疗。PIRA 结果的检测和统计分析存在挑战，增加了错误推断的风险。在解释我们的发现时，由于纳入研究的异质性较大，需要谨慎。
