Contributions
Abstract: P564
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In CLARITY, Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (RMS); efficacy was sustained in Years 3 and 4 without further treatment (CLARITY Ext). In CLARITY, patients with high disease activity (HDA) showed clinical and magnetic resonance imaging (MRI) responses to CT3.5 that were better than, or comparable to, those seen in the overall CLARITY population.
Objectives: Post hoc analysis to determine if the efficacy in patients with HDA treated with CT3.5 in CLARITY (Years 1 and 2) was sustained for the long term in patients receiving PBO in CLARITY Ext (Years 3 and 4).
Methods: This analysis used 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1. High relapse activity (HRA), defined as ≥2 relapses during the year before study entry whether on disease modifying drug (DMD) treatment or not; 2. HRA plus disease activity on treatment (DAT), defined as ≥1 relapse during the year before study entry while on therapy with other DMDs AND ≥1 T1 gadolinium‑enhancing (Gd+) or ≥9 T2 lesions. Clinical and MRI outcomes were analysed for patients (N=806) randomised to CLARITY Ext who fulfilled HRA and HRA+DAT criteria at CLARITY baseline and who received CT3.5 in CLARITY and PBO in CLARITY Ext.
Results: The annualised relapse rate (ARR) for qualifying relapses in CLARITY Ext for the population who switched to placebo in Ext from CT3.5 in CLARITY (N=98) was 0.15 (95% confidence interval [CI]; 0.11, 0.21). ARRs for HRA (N=29) and non-HRA (N=69) were 0.15 (95%CI; 0.08, 0.28) and 0.15 (95%CI; 0.10, 0.22), respectively. For HRA+DAT (N=31) and non-HRA+DAT (N=67), ARRs were 0.14 (95%CI; 0.08, 0.26) and 0.15 (95%CI; 0.10, 0.22). The ARRs in this analysis were similar to those seen for the HDA subgroups in CLARITY. In this study, fewer patients in the HDA subgroups had confirmed 3-month Expanded Disability Status Scale (EDSS) progression relative to non-HDA and overall groups (overall population: 18%; HRA and non-HRA: 14% and 20%, respectively; HRA+DAT and non-HRA+DAT: 13% and 21%, respectively). The proportion of patients with confirmed 3- and 6-month EDSS progression was lower in HDA subgroups in CLARITY Ext compared to corresponding subgroups in CLARITY.
Conclusions: In CLARITY Ext, long-term sustainability of the clinical effect was observed in HDA patients who were treated with CT3.5 in CLARITY.
Disclosure: CLARITY: NCT00213135; CLARITY Extension: NCT00641537
Disclosures: 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). Author disclosures: PV 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. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, 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. PSS has served on 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; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme. BK is an employee of Merck KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd., a division of Merck KGaA, Darmstadt, Germany.
Abstract: P564
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In CLARITY, Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (RMS); efficacy was sustained in Years 3 and 4 without further treatment (CLARITY Ext). In CLARITY, patients with high disease activity (HDA) showed clinical and magnetic resonance imaging (MRI) responses to CT3.5 that were better than, or comparable to, those seen in the overall CLARITY population.
Objectives: Post hoc analysis to determine if the efficacy in patients with HDA treated with CT3.5 in CLARITY (Years 1 and 2) was sustained for the long term in patients receiving PBO in CLARITY Ext (Years 3 and 4).
Methods: This analysis used 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1. High relapse activity (HRA), defined as ≥2 relapses during the year before study entry whether on disease modifying drug (DMD) treatment or not; 2. HRA plus disease activity on treatment (DAT), defined as ≥1 relapse during the year before study entry while on therapy with other DMDs AND ≥1 T1 gadolinium‑enhancing (Gd+) or ≥9 T2 lesions. Clinical and MRI outcomes were analysed for patients (N=806) randomised to CLARITY Ext who fulfilled HRA and HRA+DAT criteria at CLARITY baseline and who received CT3.5 in CLARITY and PBO in CLARITY Ext.
Results: The annualised relapse rate (ARR) for qualifying relapses in CLARITY Ext for the population who switched to placebo in Ext from CT3.5 in CLARITY (N=98) was 0.15 (95% confidence interval [CI]; 0.11, 0.21). ARRs for HRA (N=29) and non-HRA (N=69) were 0.15 (95%CI; 0.08, 0.28) and 0.15 (95%CI; 0.10, 0.22), respectively. For HRA+DAT (N=31) and non-HRA+DAT (N=67), ARRs were 0.14 (95%CI; 0.08, 0.26) and 0.15 (95%CI; 0.10, 0.22). The ARRs in this analysis were similar to those seen for the HDA subgroups in CLARITY. In this study, fewer patients in the HDA subgroups had confirmed 3-month Expanded Disability Status Scale (EDSS) progression relative to non-HDA and overall groups (overall population: 18%; HRA and non-HRA: 14% and 20%, respectively; HRA+DAT and non-HRA+DAT: 13% and 21%, respectively). The proportion of patients with confirmed 3- and 6-month EDSS progression was lower in HDA subgroups in CLARITY Ext compared to corresponding subgroups in CLARITY.
Conclusions: In CLARITY Ext, long-term sustainability of the clinical effect was observed in HDA patients who were treated with CT3.5 in CLARITY.
Disclosure: CLARITY: NCT00213135; CLARITY Extension: NCT00641537
Disclosures: 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). Author disclosures: PV 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. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, 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. PSS has served on 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; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme. BK is an employee of Merck KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd., a division of Merck KGaA, Darmstadt, Germany.