Reduction in CUA MRI Lesions in the First 6 Months after Cladribine Tablets Treatment for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS Subgroup Analysis
Nicola De Stefano1, Frederik Barkhof2,3, Xavier Montalban4, Anat Achiron5, Tobias Derfuss6, Andrew Chan7, Suzanne Hodgkinson8, Alexandre Prat9, Letizia Leocani10, Klaus Schmierer11,12, Finn Sellebjerg13, Patrick Vermersch14, Heinz Wiendl15, Birgit Keller16, Sanjeev Roy17
1Department of Neurological and Behavioural Sciences, University of Siena, 2Department of Radiology, VU University Medical Center, 3UCL Institute of Neurology, 4Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, 5Multiple Sclerosis Center, Sheba Academic Medical Center, 6Department of Neurology, University Hospital Basel, 7University Hospital of Berne, University of Berne, 8Ingham Institute for Applied Medical Research, University of New South Wales Medicine, 9Department of Neurosciences, Université de Montréal, 10Experimental Neurophysiology, University Vita-Salute San Raffaele, INSPE, 11Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, 12Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, 13Danish MS Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 14University of Lille, Inserm U1172 LilNCog, CHU Lille, FHU Imminent, 15Department of Neurology, Institute of Translational Neurology, University of Münster, 16Merck KGaA, Darmstadt, Germany, 17Merck, Aubonne, Switzerland, a division of Merck KGaA, Darmstadt, Germany
Objective:
To report the onset of action of cladribine tablets, 3.5 mg/kg over 2 years (CT3.5), in patients with highly active relapsing multiple sclerosis (RMS) by observing changes in counts of combined unique active (CUA) lesions during the first 6 months of MAGNIFY-MS (NCT03364036), according to patient subgroups.
Background:
With early and frequent magnetic resonance imaging (MRI), MAGNIFY-MS will provide valuable insights into the onset of action of CT3.5.
Design/Methods:
Subgroups included: high relapse activity (HRA)/non-HRA, treatment naïve/prior disease-modifying drug (DMD) treatment, and CUA lesion count >0 at baseline. MRI scans for all subgroups were performed during the baseline period (screening-baseline) and at Months 1, 2, 3, and 6 following CT3.5 treatment. Differences in CUA lesion count for post-baseline periods (Period 1: Months 1–6; Period 2: Months 2–6; Period 3: Months 3–6) were compared with the baseline period. CUA lesions were standardized to period length and number of MRIs in a period. A mixed-effects linear regression model was used to account for within pooled center correlation, and adjusted for standardized CUA lesion count during the baseline period, age, and baseline Expanded Disability Status Scale (>3, ≤3).
Results:
Changes from baseline to Periods 3, 2, and 1, respectively, for least squares mean estimates of standardized CUA lesion counts were: HRA patients, -2.018, -1.801, -1.446; non-HRA, -1.201,
-1.057, -0.827; treatment naïve, -1.460, -1.316, -1.092; prior DMD treatment, -1.876, -1.637, -1.269; CUA lesion count >0 at baseline, -3.132, -2.790, -2.253. For all subgroups, standardized CUA lesion counts reduced in all 3 periods (P<0.0001 all) compared with baseline.
Conclusions:
Treatment with CT3.5 demonstrated an early onset of action, irrespective of patients’ baseline relapse activity or prior DMD history. In the first 6 months, on average, CUA lesions were reduced versus baseline between the first scan at end of month 1 and end of month 6.