Freedman Mark S, Coyle Patricia K, Comi Giancarlo, L Scarberry Susan, Damian Doris, Hyvert Yann, Dangond Fernando, Galazka Andrew, Jack Dominic, Lebson Lori A, Leist Thomas P
Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
Department of Neurology, Stony Brook University, Stony Brook, NY, USA.
Mult Scler J Exp Transl Clin. 2021 Feb 24;7(1):2055217321990852. doi: 10.1177/2055217321990852. eCollection 2021 Jan-Mar.
In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE).
To determine the timing of effects of cladribine tablets on lesion activity assessed by magnetic resonance imaging (MRI).
This analysis assessed the effect of cladribine tablets versus placebo in ORACLE-MS on secondary MRI endpoints including T1 gadolinium-enhancing (Gd+), new or enlarging T2 lesions, and combined unique active lesions assessed on MRI scans performed at screening and every 3 months thereafter.
Compared to placebo, cladribine tablets 3.5 mg/kg treatment appeared to lead to a trend of reductions in the mean number of T1 Gd+ lesions by Week 13 (first post-baseline scan: 0.37 vs. 1.00), new or enlarging T2 (0.20 vs. 1.01) and combined unique active (0.29 vs. 1.91) lesions by Week 24. Low lesion counts were maintained with cladribine tablets throughout 96 weeks. Similar results were observed with the 5.25 mg/kg dosage.
In participants with an FCDE, cladribine tablets appeared to reduce lesion numbers within 13 weeks (time of first evaluation).
在3期、为期96周的ORACLE-MS研究中，对于首次发生临床脱髓鞘事件（FCDE）的参与者，10毫克克拉屈滨片（两年累积剂量为3.5或5.25毫克/千克）与安慰剂相比，显著减少了与多发性硬化相关的病灶。
确定克拉屈滨片对通过磁共振成像（MRI）评估的病灶活动的影响时间。
本分析评估了ORACLE-MS研究中克拉屈滨片与安慰剂对次要MRI终点的影响，这些终点包括T1钆增强（Gd+）、新出现或扩大的T2病灶，以及在筛查时及此后每3个月进行的MRI扫描中评估的合并独特活动性病灶。
与安慰剂相比，3.5毫克/千克治疗剂量的克拉屈滨片在第13周时似乎导致T1 Gd+病灶平均数量有减少趋势（首次基线后扫描：0.37对1.00），在第24周时新出现或扩大的T2病灶（0.20对1.01）以及合并独特活动性病灶（0.29对1.91）有减少趋势。在整个96周内，克拉屈滨片的病灶计数一直维持在低水平。5.25毫克/千克剂量也观察到类似结果。
在患有FCDE的参与者中，克拉屈滨片似乎在13周内（首次评估时）减少了病灶数量。
