ECTRIMS eLearning

Benefits of cladribine tablets on the achievement of no evidence of disease activity (NEDA) status in patients with multiple sclerosis: analysis of pooled double-blind data from the CLARITY and ONWARD studies
Author(s): ,
G Giovannoni
Affiliations:
Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom
,
X Montalban
Affiliations:
Department of Neurology-Neuroimmunology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
,
C Hicking
Affiliations:
Merck KGaA, Darmstadt, Germany
F Dangond
Affiliations:
EMD Serono, Inc., Billerica, MA, United States
ECTRIMS Learn. Giovannoni G. 09/15/16; 146481; P641
Prof. Gavin Giovannoni
Prof. Gavin Giovannoni
Contributions Biography
Abstract

Abstract: P641

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy vs placebo across a spectrum of patients with active multiple sclerosis. Combining efficacy data from the double-blind periods of these studies enables the effects of 2 years" treatment with cladribine tablets (3.5mg/kg cumulative dose) on the proportion of patients with no evidence of disease activity (NEDA) to be assessed.

Objective: To summarise proportions of patients with no evidence of disease activity in patients with relapsing MS (RMS) treated with cladribine tablets 3.5mg/kg, including various subgroups, in the CLARITY and ONWARD studies.

Methods: Data from the 2-year, double-blind periods of CLARITY and ONWARD were used to summarise the efficacy of cladribine tablets 3.5mg/kg in patients with RMS (n=1067), and in subgroups defined by baseline characteristics. ONWARD subjects on cladribine or placebo were also taking IFN-beta. Data for patients achieving NEDA (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no new or enhancing T1 Gd+ lesions and no new or active T2 lesions), were compared using odds ratios (OR) and 95% confidence intervals (95% CI) for patients treated with cladribine tablets 3.5mg/kg or placebo. Subgroups analysed included: patients with no T1 Gd+ lesions (n=759) or with ≥1 T1 Gd+ lesions (n=308); EDSS score ≤3.0 (n=653) or ≥3.5 (n=414). Additional analyses included subgroups of patients with/without high disease activity; 0 or ≥1 relapse in the prior 12 months; < 9 or ≥9 T2 lesions; prior or no prior use of disease modifying drugs; males or females and age ≤40 or >40 years

(not described here).

Results: Cladribine tablets 3.5mg/kg showed consistent benefits vs placebo in the proportion of patients achieving NEDA in the overall population (OR [95% CI]: 3.95 [2.90-5.37]) and in the subgroups: no T1 Gd+ lesions OR: 3.82 (2.71-5.38), ≥1 T1 Gd+ lesions OR: 8.12 (3.31-19.90), EDSS ≤3.0 OR 4.36 (2.90-6.56), EDSS ≥3.5 OR 3.48 (2.17-5.57).

Conclusions: Analysis of pooled data from CLARITY and ONWARD showed that cladribine tablets 3.5mg/kg significantly increased the proportion of patients with no evidence of disease activity compared with placebo in a population of patients with active RMS. Compared with placebo, cladribine tablets also showed significant increases in the proportion of patients with no evidence of disease activity across a range of patient subgroups.

Disclosure: 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).

Gavin Giovannoni serves on advisory boards for Merck, Biogen Idec, and Vertex Pharmaceuticals; has received speaker honoraria and consulting fees from Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharma, Merck, Biogen Idec, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Genzyme Corporation, Ironwood, and Novartis; serves on the Merck speakers bureau; and received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.

Xavier Montalban has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.

Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.

Fernando Dangond is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.

Abstract: P641

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy vs placebo across a spectrum of patients with active multiple sclerosis. Combining efficacy data from the double-blind periods of these studies enables the effects of 2 years" treatment with cladribine tablets (3.5mg/kg cumulative dose) on the proportion of patients with no evidence of disease activity (NEDA) to be assessed.

Objective: To summarise proportions of patients with no evidence of disease activity in patients with relapsing MS (RMS) treated with cladribine tablets 3.5mg/kg, including various subgroups, in the CLARITY and ONWARD studies.

Methods: Data from the 2-year, double-blind periods of CLARITY and ONWARD were used to summarise the efficacy of cladribine tablets 3.5mg/kg in patients with RMS (n=1067), and in subgroups defined by baseline characteristics. ONWARD subjects on cladribine or placebo were also taking IFN-beta. Data for patients achieving NEDA (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no new or enhancing T1 Gd+ lesions and no new or active T2 lesions), were compared using odds ratios (OR) and 95% confidence intervals (95% CI) for patients treated with cladribine tablets 3.5mg/kg or placebo. Subgroups analysed included: patients with no T1 Gd+ lesions (n=759) or with ≥1 T1 Gd+ lesions (n=308); EDSS score ≤3.0 (n=653) or ≥3.5 (n=414). Additional analyses included subgroups of patients with/without high disease activity; 0 or ≥1 relapse in the prior 12 months; < 9 or ≥9 T2 lesions; prior or no prior use of disease modifying drugs; males or females and age ≤40 or >40 years

(not described here).

Results: Cladribine tablets 3.5mg/kg showed consistent benefits vs placebo in the proportion of patients achieving NEDA in the overall population (OR [95% CI]: 3.95 [2.90-5.37]) and in the subgroups: no T1 Gd+ lesions OR: 3.82 (2.71-5.38), ≥1 T1 Gd+ lesions OR: 8.12 (3.31-19.90), EDSS ≤3.0 OR 4.36 (2.90-6.56), EDSS ≥3.5 OR 3.48 (2.17-5.57).

Conclusions: Analysis of pooled data from CLARITY and ONWARD showed that cladribine tablets 3.5mg/kg significantly increased the proportion of patients with no evidence of disease activity compared with placebo in a population of patients with active RMS. Compared with placebo, cladribine tablets also showed significant increases in the proportion of patients with no evidence of disease activity across a range of patient subgroups.

Disclosure: 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).

Gavin Giovannoni serves on advisory boards for Merck, Biogen Idec, and Vertex Pharmaceuticals; has received speaker honoraria and consulting fees from Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharma, Merck, Biogen Idec, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Genzyme Corporation, Ironwood, and Novartis; serves on the Merck speakers bureau; and received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.

Xavier Montalban has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.

Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.

Fernando Dangond is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.

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