Abstract: P1164
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In the CLARITY study, treatment with cladribine tablets (CT) vs placebo (PBO) showed strong efficacy in a large cohort of patients with RMS over 2 years. Patients with high disease activity (HDA) are at higher risk of relapses and disability progression.
Objective: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs PBO on outcomes assessed by magnetic resonance imaging (MRI) in subgroups of CLARITY patients with evidence of HDA at study entry, using two HDA definitions.
Methods: CLARITY patients randomised to CT3.5 or PBO were retrospectively analysed using two sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1. high relapse activity (HRA), which was defined as ≥2 relapses during the year before study entry whether on DMD treatment or not 2. HRA plus treatment non-response (HRA+TNR) in which TNR was defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the year before study entry while on therapy with other DMDs.
Results: For cumulative new T1 Gd+ lesions, the relative risk ratio (RRR) in the HRA subgroup (0.087, 95%CI:0.052;0.144) was significantly lower in favour of CT3.5 (n=130) over PBO (n=131, p< 0.0001). In the HRA+TNR subgroup, the RRR (0.077, 95%CI:0.046;0.128) also significantly favoured CT3.5 (n=140) vs. PBO (n=149, p< 0.0001). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097, 95%CI:0.070;0.134, p< 0.0001). For cumulative active T2 lesions, the RRR also significantly favoured CT3.5 vs. PBO for HRA (0.263, 95%CI:0.180;0.383, p< 0.0001) and HRA+TNR (0.254, 95%CI:0.178;0.363, p< 0.0001): risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272, 95%CI:0.221;0.335, p< 0.0001). The RRR for cumulative combined unique (CU) lesions significantly favoured CT3.5 vs. PBO for HRA (0.212, 95%CI:0.145;0.311, p< 0.0001) and HRA+TNR (0.203, 95%CI:0.141;0.291, p< 0.0001): risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234, 95%CI:0.190;0.290, p< 0.0001). Comparable results were seen in the non-HDA counterparts, with no significant interactions between HDA and non-HDA subgroups.
Conclusions: In patients with RMS selected using HDA criteria in the CLARITY study, treatment with CT3.5 produced comparable efficacy in reducing MRI markers of disease activity to the overall study population.
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).
GG: 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.
KR: has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda and Roche/Genentech.
SC: has received honoraria for lectures/consultations from Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GC: 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 Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
PR: 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.
PS-S: 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.
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.
CH: is an employee of Merck KGaA, Darmstadt, Germany.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
Abstract: P1164
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In the CLARITY study, treatment with cladribine tablets (CT) vs placebo (PBO) showed strong efficacy in a large cohort of patients with RMS over 2 years. Patients with high disease activity (HDA) are at higher risk of relapses and disability progression.
Objective: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs PBO on outcomes assessed by magnetic resonance imaging (MRI) in subgroups of CLARITY patients with evidence of HDA at study entry, using two HDA definitions.
Methods: CLARITY patients randomised to CT3.5 or PBO were retrospectively analysed using two sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1. high relapse activity (HRA), which was defined as ≥2 relapses during the year before study entry whether on DMD treatment or not 2. HRA plus treatment non-response (HRA+TNR) in which TNR was defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the year before study entry while on therapy with other DMDs.
Results: For cumulative new T1 Gd+ lesions, the relative risk ratio (RRR) in the HRA subgroup (0.087, 95%CI:0.052;0.144) was significantly lower in favour of CT3.5 (n=130) over PBO (n=131, p< 0.0001). In the HRA+TNR subgroup, the RRR (0.077, 95%CI:0.046;0.128) also significantly favoured CT3.5 (n=140) vs. PBO (n=149, p< 0.0001). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097, 95%CI:0.070;0.134, p< 0.0001). For cumulative active T2 lesions, the RRR also significantly favoured CT3.5 vs. PBO for HRA (0.263, 95%CI:0.180;0.383, p< 0.0001) and HRA+TNR (0.254, 95%CI:0.178;0.363, p< 0.0001): risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272, 95%CI:0.221;0.335, p< 0.0001). The RRR for cumulative combined unique (CU) lesions significantly favoured CT3.5 vs. PBO for HRA (0.212, 95%CI:0.145;0.311, p< 0.0001) and HRA+TNR (0.203, 95%CI:0.141;0.291, p< 0.0001): risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234, 95%CI:0.190;0.290, p< 0.0001). Comparable results were seen in the non-HDA counterparts, with no significant interactions between HDA and non-HDA subgroups.
Conclusions: In patients with RMS selected using HDA criteria in the CLARITY study, treatment with CT3.5 produced comparable efficacy in reducing MRI markers of disease activity to the overall study population.
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).
GG: 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.
KR: has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda and Roche/Genentech.
SC: has received honoraria for lectures/consultations from Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GC: 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 Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
PR: 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.
PS-S: 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.
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.
CH: is an employee of Merck KGaA, Darmstadt, Germany.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.