@article{53ca6657f110434cbb9fcd91698917ef,
title = "Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study",
abstract = "Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Objective: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Methods: Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). Results: In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Conclusion: Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.",
keywords = "Cladribine Tablets, efficacy, high disease activity, risk:benefit, safety",
author = "Gavin Giovannoni and {Soelberg Sorensen}, Per and Stuart Cook and Rammohan, {Kottil W.} and Peter Rieckmann and Giancarlo Comi and Fernando Dangond and Christine Hicking and Patrick Vermersch",
note = "Funding Information: The authors would like to thank patients and their families, investigators, co-investigators and the study teams at each of the participating centres and at Merck KGaA, Darmstadt, Germany. Medical writing assistance was provided by Mark O{\textquoteright}Connor of inScience Communications, Springer Healthcare, Chester, UK, and was funded by Merck KGaA, Darmstadt, Germany. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/ or publication of this article: G.G. has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood and Novartis and has received research support unrelated to this study from Biogen Idec, Merck, Novartis and Ironwood. P.S.S. has served on the advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals and GSK; on steering committees or independent data-monitoring boards in trials sponsored by Merck, Teva, GSK and Novartis and has received speaker honoraria from Biogen Idec, Merck, Teva, Sanofi-Aventis, Genzyme and Novartis. His department has received research support from 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; has served on the advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals and Biogen Idec and received grant support from Bayer HealthCare. K.W.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, Receptors, Biogen Idec, Genentech-Roche and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Merck, Biogen Domp{\`e}, Bayer Schering and Serono Symposia International Foundation and trial grant support from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Domp{\`e} and Bayer Schering. F.D. is an 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 USA) and Merck Serono SA – Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW). Publisher Copyright: {\textcopyright} The Author(s), 2018.",
year = "2019",
month = may,
day = "1",
doi = "10.1177/1352458518771875",
language = "English (US)",
volume = "25",
pages = "819--827",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "6",
}