Abstract: P1143
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In the CLARITY study, treatment with cladribine tablets (CT) showed strong efficacy vs placebo (PBO) over 2 yrs in a large cohort of patients with RMS. Patients with HDA are at higher risk of clinical or MRI activity and disability progression; and hence less likely to attain NEDA (no relapses, MRI activity or progression).
Objective: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs PBO on the proportion of patients with NEDA in subgroups of CLARITY patients at higher risk of disease progression than the ITT population, selected using 2 HDA definitions.
Methods: Patients were retrospectively analysed using 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 yr before study entry whether on DMD treatment or not; 2 HRA plus treatment non-response (HRA+TNR) with TNR defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the yr before study entry while on therapy with other DMDs. Data for patients treated with CT 3.5 or PBO who fulfilled these criteria and achieved NEDA status (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no T1 Gd+ lesions and no active T2 lesions) were compared over the 2-yr study using odds ratios (OR) and 95% confidence intervals (95%CI).
Results: In each HDA subgroup, the proportion of patients who fulfilled individual NEDA criteria was higher with CT3.5. For example, in the HRA subgroup, 76% of CT3.5-treated patients (n=130) were relapse-free and 84% were T1 Gd+ lesion-free vs 49% and 31%, respectively, for PBO (n=131). In the HRA+TNR subgroup, 77% were relapse-free and 85% were T1 Gd+ lesion-free with CT 3.5 (n=140) vs 50% and 32%, respectively for PBO (n=149). Composite NEDA score: 43.2% of the HRA subgroup and 43.7% of the HRA+TNR subgroup in CT3.5-treated patients were disease activity free compared with 8.7%, (OR 8.02, 95%CI: 3.93;16.35, p< 0.0001) and 9.0% (OR 7.82, 95%CI:4.03;15.19, p< 0.0001) respectively, of PBO recipients. These values were significantly more favourable than each non-HDA counterpart subgroup in HRA+TNR patients. In the overall CLARITY population, the composite NEDA score also favoured CT (n=433) over PBO (n=437; OR 4.46, 95%CI:3.18;6.26, p< 0.0001).
Conclusions: In a large study of patients with active RMS, treatment with CT3.5 significantly increased the proportion of HDA patients with no evidence of disease activity compared with PBO.
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.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH: is an employee of Merck KGaA, Darmstadt, Germany.
Abstract: P1143
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: In the CLARITY study, treatment with cladribine tablets (CT) showed strong efficacy vs placebo (PBO) over 2 yrs in a large cohort of patients with RMS. Patients with HDA are at higher risk of clinical or MRI activity and disability progression; and hence less likely to attain NEDA (no relapses, MRI activity or progression).
Objective: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs PBO on the proportion of patients with NEDA in subgroups of CLARITY patients at higher risk of disease progression than the ITT population, selected using 2 HDA definitions.
Methods: Patients were retrospectively analysed using 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 yr before study entry whether on DMD treatment or not; 2 HRA plus treatment non-response (HRA+TNR) with TNR defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the yr before study entry while on therapy with other DMDs. Data for patients treated with CT 3.5 or PBO who fulfilled these criteria and achieved NEDA status (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no T1 Gd+ lesions and no active T2 lesions) were compared over the 2-yr study using odds ratios (OR) and 95% confidence intervals (95%CI).
Results: In each HDA subgroup, the proportion of patients who fulfilled individual NEDA criteria was higher with CT3.5. For example, in the HRA subgroup, 76% of CT3.5-treated patients (n=130) were relapse-free and 84% were T1 Gd+ lesion-free vs 49% and 31%, respectively, for PBO (n=131). In the HRA+TNR subgroup, 77% were relapse-free and 85% were T1 Gd+ lesion-free with CT 3.5 (n=140) vs 50% and 32%, respectively for PBO (n=149). Composite NEDA score: 43.2% of the HRA subgroup and 43.7% of the HRA+TNR subgroup in CT3.5-treated patients were disease activity free compared with 8.7%, (OR 8.02, 95%CI: 3.93;16.35, p< 0.0001) and 9.0% (OR 7.82, 95%CI:4.03;15.19, p< 0.0001) respectively, of PBO recipients. These values were significantly more favourable than each non-HDA counterpart subgroup in HRA+TNR patients. In the overall CLARITY population, the composite NEDA score also favoured CT (n=433) over PBO (n=437; OR 4.46, 95%CI:3.18;6.26, p< 0.0001).
Conclusions: In a large study of patients with active RMS, treatment with CT3.5 significantly increased the proportion of HDA patients with no evidence of disease activity compared with PBO.
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.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH: is an employee of Merck KGaA, Darmstadt, Germany.