Early Onset of Action and Sustained Efficacy of MRI Outcomes During Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-year MAGNIFY-MS Study
Nicola De Stefano1, Anat Achiron2, Frederik Barkhof3, Andrew Chan4, Tobias Derfuss5, Suzanne Hodgkinson6, Letizia Leocani7, Xavier Montalban8, Alexandre Prat9, Klaus Schmierer10, Finn Sellebjerg11, Patrick Vermersch12, Heinz Wiendl13, Birgit Keller14, Andrzej Smyk14, Lidia Gardner15
1Department of Medicine, Surgery and Neuroscience, University of Siena, 2Multiple Sclerosis Center, Sheba Academic Medical Center, 3Department of Radiology, VU University Medical Center, 4Department of Neurology, Inselspital, Bern University Hospital, University of Bern, 5Department of Neurology, Department of Neurology, University Hospital Basel, 6Ingham Institute for Applied Medical Research, University of New South Wales Medicine, 7Experimental Neurophysiology Unit, Vita-Salute San Raffaele University, 8Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d’Hebron, Universitat Autonoma de Barcelona, 9Department of Neurosciences, Université de Montréal, 10The Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, 11Danish MS Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, 12Univ. Lille, Inserm U1172 LilNCog, CHU Lille, FHU Precise, 13Department of Neurology, Institute of Translational Neurology, University of Münster, 14the healthcare business of Merck KGaA, Darmstadt, Germany, 15EMD Serono Research and Development Institute, Inc., Billerica, MA, USA
Objective:
To report the 2-year, follow-up magnetic resonance imaging (MRI), clinical, and safety results from the MAGNIFY-MS study (NCT03364036).
Background:
MAGNIFY-MS used frequent MRI to increase understanding of the onset of action and sustained efficacy of cladribine tablets (CladT) 3.5 mg/kg cumulative dose over 2 years in patients with highly active relapsing multiple sclerosis.
Design/Methods:
MRI was performed at screening, baseline, and at Months (M)1, 2, 3, 6, 12, 15, 18, and 24 following CladT initiation. Combined unique active (CUA), T1 Gd+, and new or enlarging T2 lesion count changes were compared exploratively between baseline and post-baseline visits using a mixed-effects linear model for repeated measures. Poisson regression estimated annualized relapse rate (ARR). Safety endpoints are summarized descriptively.
Results:
Overall, 270 patients received treatment (mean age 37.7 years; 66.7% female). Among evaluable patients (n=265), mean CUA lesion counts reduced significantly from M2 onwards
(-3.52 lesions/year; 95% confidence interval [CI]: -4.60, -2.43; p<0.0001). The maximum mean change was reached at M6 (-5.99 lesions/year; 95%CI: -6.18, -5.80; p<0.0001) and maintained until M24 (-5.91 lesions/year; 95%CI: -6.15, -5.67; p<0.0001). Annualized mean T1 Gd+ and new/enlarging T2 lesion counts decreased similarly. ARR was 0.11 (95%CI: 0.09, 0.15). Expanded Disability Status Scale score remained stable for most patients. Overall, 227 patients (84.1%) had ≥1 treatment-emergent adverse event (TEAE); 14 patients (5.2%) had ≥1 serious TEAE. Most post-baseline reports of lymphopenia were Grade 1-2; 66/270 patients (24.4%) experienced Grade 3 and (2/270 patients (0.7%) experienced Grade 4 lymphopenia. TEAEs leading to temporary discontinuation of study treatment occurred in 4 patients (1.5%). Six patients (7.7%) withdrew due to progressive disease.
Conclusions:
CladT shows an early onset of action from M2 onwards with sustained reductions in MRI lesion counts over 2 years. The benefit:risk profile of CladT remained unchanged and in line with previous observations.