Gavin Giovannoni1, Per Soelberg Sorensen2, Stuart Cook3, Kottil Rammohan4, Peter Rieckmann5, Giancarlo Comi6, Fernando Dangond7, Abidemi K Adeniji7, Patrick Vermersch8. 1. Department of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 2. Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Neurology & Neurosciences, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA. 4. Department of Neurosurgery, The Ohio State University Columbus, OH, USA. 5. Department of Neurology, Neurologische Klinik, Akademisches Krankenhaus Sozialstiftung Bamberg, Bamberg, Germany. 6. Department of Neurology and Institute of Experimental Neurology, Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy. 7. Department of Neurology and Immunology, EMD Serono, Inc., Billerica, MA, USA. 8. Department of Neurosurgery, CHU Lille, Université de Lille, Lille, France.
Abstract
BACKGROUND: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. METHODS: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. RESULTS: A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. CONCLUSION:Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.
RCT Entities:
BACKGROUND: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. METHODS: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. RESULTS: A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. CONCLUSION:Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.
Authors: Alexandra van Wijnen; Franca Petrov; Michelle Maiworm; Stefan Frisch; Christian Foerch; Elke Hattingen; Helmuth Steinmetz; Johannes C Klein; Ralf Deichmann; Marlies Wagner; René-Maxime Gracien Journal: Eur Radiol Date: 2019-10-10 Impact factor: 5.315
Authors: Jiwon Oh; Bryan Walker; Gavin Giovannoni; Dominic Jack; Fernando Dangond; Axel Nolting; Julie Aldridge; Lori A Lebson; Thomas P Leist Journal: Mult Scler J Exp Transl Clin Date: 2021-07-13