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Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study
Xavier Montalban1, Thomas P Leist1, Bruce A Cohen1
1Department of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Objective:
To evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment.
Methods:
A 96-week phase II study, randomizing patients treated with IFN-β to cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β. Patients were to receive cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β in a 2:1 ratio (n = 172) with safety and exploratory efficacy outcomes being assessed.
Results:
Adverse events (AEs) and serious AEs were similar across treatment groups, except lymphopenia. Fifty of 124 (40.3%) cladribine/IFN-β recipients vs 0% of placebo/IFN-β recipients reported lymphopenia as an AE, with grade 3/4 lymphopenia (laboratory lymphocyte count < 500 cells/mm3) experienced by 79/124 (63.7%) vs 1 (2.1%), respectively. Patients treated with cladribine tablets 3.5 mg/kg/IFN-β were 63% less likely to have a qualifying relapse than placebo/IFN-β recipients, and cladribine tablets 3.5 mg/kg/IFN-β reduced most MRI measures of disease activity.
Conclusions:
In patients with active relapsing MS despite IFN-β treatment, cladribine tablets 3.5 mg/kg/IFN-β reduced relapses and MRI lesion activity over 96 weeks compared with placebo/IFN-β but led to an increased incidence of lymphopenia.
Classification Of Evidence:
This study provides Class I evidence that for patients with active relapsing MS despite IFN-β treatment, cladribine tablets added to IFN-β reduced relapses and MRI lesion activity over 96 weeks and increased the incidence of lymphopenia.
Clinical Trial Registration:
NCT00436826.
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