088 Cladribine tablets were associated with rapid onset of improvements in MRI outcomes in the ORACLE-MS trial. (29th July 2019)

• Record Type: Journal Article
• Authors: Gillett, Alan; Scarberry, Susan; Damian, Doris; Hyvert, Yann; Dangond, Fernando; Lebson, Lori; Leist, Thomas
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90(2019)e7
• Page Start: A28
• Page End: A28
• Publication Date: 2019-07-29
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-anzan.76
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Introduction: In ORACLE-MS (616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis), cladribine tablets (CT) 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly delayed the time-to-conversion to clinically definite multiple sclerosis (CDMS), and reduced new/persisting T1 gadolinium-enhancing (T1 Gd+), new/enlarged or active T2 and combined unique active (CUA) lesion number. Here, the timing of CT effect is evaluated. Methods: MRI scans were performed at screening and every 12 weeks, for non-converting CDMS subjects. MRI-based endpoints were analyzed using analysis of covariance (ANCOVA) and negative binomial models. The temporal effects of the first yearly treatment course of CT and placebo on T1 Gd+, active T2, and CUA lesions were evaluated. Results: 96 weeks: the reduction in mean T1 Gd+, active T2, or CUA lesion number per patient per scan was nominally significantly greater for CT versus placebo (p<0.0001). Early change in Gd+ lesion volume (at Week 13) from baseline was CT, -155.73 mm 3 ; placebo, -14.76 mm 3 . Comparatively larger reductions in mean active T2 and CUA lesion numbers with CT at Week 13 versus placebo were observed (active T2: CT, -1.25; placebo, -1.43; CUA: CT, -1.56; placebo, -2.41). The mean number of T1 Gd+ lesions at 13 weeks following CT was 0.37 versus 1.0 with placebo. Conclusions: MRI data from ORACLE-MS subjects suggest the first yearly treatment course of CT has a rapid onset of action, with beneficial treatment effects on active lesion number and volume evident by Week 13.