Abstract: 164
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cladribine tablets (CT), given annually for 2 years in short-duration courses in CLARITY, significantly reduced relapse rates and slowed disability progression in patients with relapsing multiple sclerosis (RMS). After a treatment gap (median duration ~41 weeks), the CLARITY Extension (EXT) study compared the effects of 2 years" additional CT treatment vs no additional treatment.
Objective: To assess efficacy in patients treated with 2 courses of CT or placebo (PBO) in CLARITY and 2 additional courses of CT or PBO in CLARITY EXT.
Methods: In CLARITY EXT, patients with RMS who had received PBO in CLARITY were assigned to CT 3.5mg/kg body weight; those treated with CT (3.5 or 5.25mg/kg) were re-randomised 2:1 to CT 3.5mg/kg or PBO. Annualised relapse rates (ARR) and the proportions of patients qualifying relapse free were compared for CLARITY vs CLARITY EXT in: patients who received CT 3.5mg/kg in CLARITY and PBO in CLARITY EXT (CP 3.5mg/kg; n=90); CT 3.5mg/kg in CLARITY and CT 3.5mg/kg in CLARITY EXT
(CC 7mg/kg; n=165); CT 5.25mg/kg in CLARITY and CT 3.5mg/kg in CLARITY EXT (CC 8.75mg/kg; n=172); PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg; n=226). Proportions of patients free from 3- or 6-month confirmed disability progression (CDP) were also assessed during CLARITY EXT only.
Results: There were no significant differences in ARR for CLARITY vs CLARITY EXT except in patients who received PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg, 0.26 vs 0.10,
p< 0.0001). The proportion of patients who qualified relapse free was >70% and was similar between CLARITY vs CLARITY EXT across all groups, except patients treated with PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg, 58.0% vs 79.6%, p< 0.0001). The proportion of patients without confirmed 3-m CDP in CLARITY EXT ranged from 81.6 to 90.2%, and the proportion without confirmed 6-m CDP ranged from 86.7 to 93.5%.
Conclusions: Comparing CLARITY vs CLARITY EXT demonstrates the durable efficacy of CT: clinical benefits (lower relapse rates) were maintained in patients who received CT in CLARITY and PBO in CLARITY EXT. In patients who received CT in CLARITY and CT in CLARITY EXT, no additional clinical benefit was seen with two further courses of CT compared to patients who received CT only in CLARITY. For patients who received PBO in CLARITY, switching to CT in CLARITY EXT significantly reduced ARR and increased the proportion of relapse-free patients.
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.
Giancarlo Comi has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, 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, Merck, Biogen Dompè, and Bayer Schering.
Stuart Cook 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.
Peter Rieckmann 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.
Kottil Rammohan has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda and Roche/Genentech.
Per Soelberg-Sorensen has served on advisory boards for Biogen Idec, Merck, Novartis, Genmab, Teva, Elan, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Genmab, Teva, GSK, and Bayer Schering; has served as Editor-in-Chief of the European Journal of Neurology, is currently editorial board member for Multiple Sclerosis Journal, European Journal of Neurology, and Therapeutic Advances in Neurological Disorders; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Bayer Schering, Sanofi-Aventis, Genzyme, and Novartis; and has received payment for writing/reviewing manuscripts from IBI Consulting, a division of Informa plc. His department has received research support from Biogen Idec, Bayer Schering, Merck Serono, Teva, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health.
Patrick Vermersch has received honoraria and consulting fees from Biogen Idec, Sanofi, Bayer, Novartis, Merck, GSK, and Almirall; and research support from Biogen Idec, Sanofi, Bayer, and Merck.
Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.
Abidemi Adeniji and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Abstract: 164
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cladribine tablets (CT), given annually for 2 years in short-duration courses in CLARITY, significantly reduced relapse rates and slowed disability progression in patients with relapsing multiple sclerosis (RMS). After a treatment gap (median duration ~41 weeks), the CLARITY Extension (EXT) study compared the effects of 2 years" additional CT treatment vs no additional treatment.
Objective: To assess efficacy in patients treated with 2 courses of CT or placebo (PBO) in CLARITY and 2 additional courses of CT or PBO in CLARITY EXT.
Methods: In CLARITY EXT, patients with RMS who had received PBO in CLARITY were assigned to CT 3.5mg/kg body weight; those treated with CT (3.5 or 5.25mg/kg) were re-randomised 2:1 to CT 3.5mg/kg or PBO. Annualised relapse rates (ARR) and the proportions of patients qualifying relapse free were compared for CLARITY vs CLARITY EXT in: patients who received CT 3.5mg/kg in CLARITY and PBO in CLARITY EXT (CP 3.5mg/kg; n=90); CT 3.5mg/kg in CLARITY and CT 3.5mg/kg in CLARITY EXT
(CC 7mg/kg; n=165); CT 5.25mg/kg in CLARITY and CT 3.5mg/kg in CLARITY EXT (CC 8.75mg/kg; n=172); PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg; n=226). Proportions of patients free from 3- or 6-month confirmed disability progression (CDP) were also assessed during CLARITY EXT only.
Results: There were no significant differences in ARR for CLARITY vs CLARITY EXT except in patients who received PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg, 0.26 vs 0.10,
p< 0.0001). The proportion of patients who qualified relapse free was >70% and was similar between CLARITY vs CLARITY EXT across all groups, except patients treated with PBO in CLARITY and CT 3.5mg/kg in CLARITY EXT (PC 3.5mg/kg, 58.0% vs 79.6%, p< 0.0001). The proportion of patients without confirmed 3-m CDP in CLARITY EXT ranged from 81.6 to 90.2%, and the proportion without confirmed 6-m CDP ranged from 86.7 to 93.5%.
Conclusions: Comparing CLARITY vs CLARITY EXT demonstrates the durable efficacy of CT: clinical benefits (lower relapse rates) were maintained in patients who received CT in CLARITY and PBO in CLARITY EXT. In patients who received CT in CLARITY and CT in CLARITY EXT, no additional clinical benefit was seen with two further courses of CT compared to patients who received CT only in CLARITY. For patients who received PBO in CLARITY, switching to CT in CLARITY EXT significantly reduced ARR and increased the proportion of relapse-free patients.
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.
Giancarlo Comi has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, 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, Merck, Biogen Dompè, and Bayer Schering.
Stuart Cook 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.
Peter Rieckmann 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.
Kottil Rammohan has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda and Roche/Genentech.
Per Soelberg-Sorensen has served on advisory boards for Biogen Idec, Merck, Novartis, Genmab, Teva, Elan, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Genmab, Teva, GSK, and Bayer Schering; has served as Editor-in-Chief of the European Journal of Neurology, is currently editorial board member for Multiple Sclerosis Journal, European Journal of Neurology, and Therapeutic Advances in Neurological Disorders; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Bayer Schering, Sanofi-Aventis, Genzyme, and Novartis; and has received payment for writing/reviewing manuscripts from IBI Consulting, a division of Informa plc. His department has received research support from Biogen Idec, Bayer Schering, Merck Serono, Teva, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, the European Union Sixth Framework Programme: Life sciences, Genomics and Biotechnology for health.
Patrick Vermersch has received honoraria and consulting fees from Biogen Idec, Sanofi, Bayer, Novartis, Merck, GSK, and Almirall; and research support from Biogen Idec, Sanofi, Bayer, and Merck.
Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.
Abidemi Adeniji and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.