@article{51faec7aa15a4bb59a4f7fa65508aa32,
title = "Safety and efficacy of cladribine tablets in patients with relapsing–remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study",
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{\textquoteright} 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.",
keywords = "CLARITY Extension, Relapsing–remitting multiple sclerosis, cladribine tablets, efficacy, randomized trial, safety",
author = "Gavin Giovannoni and {Soelberg Sorensen}, Per and Stuart Cook and Kottil Rammohan and Peter Rieckmann and Giancarlo Comi and Fernando Dangond and Adeniji, {Abidemi K.} and Patrick Vermersch",
note = "Funding Information: The authors would like to thank the patients, investigators, co-investigators involved in the trial, as well as study teams at the participating centers, at Merck KGaA, Darmstadt, Germany, and Merck Switzerland. The authors also thank Bettina Stubinski for study coordination; Nathalie Lachenal (previously of Merck Switzerland, Geneva, Switzerland), Sanjeev Anand (Merck KGaA, Darmstadt, Germany) for monitoring and assessing safety data; and Emily Martin (EMD Serono, Inc., Billerica, MA, USA) and Patrick Engrand (Cytel, Inc., Geneva, Switzerland) for data statistical analyses. In addition, the authors thank Phil Jones of inScience Communications, Chester, UK, for medical writing support, funded by Merck KGaA, Darmstadt, Germany. Clinical trial registration: NCT00641537. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the United States), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (rest of the world). Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany (in the United States), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (rest of the world). Funding Information: Biogen, Merck, Teva, Novartis, Roche, and Genzyme. S.C. has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed, Inc.; and has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare. K.R. has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech. P.R. has received honoraria for lectures/steering committee meetings from Merck, Biogen Idec, Bayer Schering Pharma, Boehringer Ingelheim, Sanofi-Aventis, Genzyme, Novartis, Teva Pharmaceutical Industries, and Serono Symposia International Foundation. G.C. has received consulting fees from Novartis, Teva Pharmaceutical Industries, Ltd, Sanofi-Aventis, Merck, Receptos, Biogen Idec, Genentech– Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind., Ltd, Sanofi-Aventis, Merck, Biogen Domp{\`e}, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind., Ltd, Sanofi-Aventis, Receptos, Biogen Idec, Genentech–Roche, Merck, Biogen Domp{\`e}, and Bayer Schering. F.D. and A.K.A. are employees of EMD Serono, Inc., a business of Merck KGaA, Billerica, MA, USA. P.V. has received honoraria or consulting fees from Biogen, Sanofi Genzyme, Bayer, Novartis, Merck, GSK, Roche, and Almirall; and research support from Biogen, Sanofi Genzyme, Bayer, and Merck. Publisher Copyright: {\textcopyright} The Author(s), 2017.",
year = "2018",
month = oct,
day = "1",
doi = "10.1177/1352458517727603",
language = "English (US)",
volume = "24",
pages = "1594--1604",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "12",
}