Abstract: P636
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cladribine tablets (CT), given annually for 2 years in short-duration courses in CLARITY, significantly improved clinical (relapses and disability progression) and MRI outcomes, and freedom from disease activity in patients with relapsing multiple sclerosis (RMS) vs placebo (PBO). After a treatment gap (median duration ~41 weeks), the CLARITY Extension (EXT) study compared the safety and efficacy of 2 years" additional CT treatment vs no additional treatment. Analysis of CLARITY EXT may provide insights into the proportions of patients remaining free from various markers of disease activity.
Objective: Separate analyses of proportions of patients free from qualifying relapses, confirmed disability progression (CDP), new T1 Gd+ or combined unique (CU) lesions in CLARITY EXT.
Methods: In CLARITY EXT, patients who received PBO in CLARITY were assigned to CT 3.5mg/kg body weight; those who received CT (3.5 or 5.25mg/kg) were re-randomised 2:1 to CT 3.5mg/kg or PBO, resulting in 5 groups: CP 3.5 (CT 3.5mg/kg in CLARITY/PBO in CLARITY EXT, n=98); CP 5.25 (CT 5.25mg/kg in CLARITY/PBO in CLARITY EXT, n=92); CC 7.0 (CT 3.5mg/kg in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=186); CC 8.75 (CT 5.25mg/kg in CLARITY/ CT 3.5mg/kg CLARITY EXT, n=186); PC 3.5 (PBO in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=244). Results are presented for the proportions of patients qualifying relapse free, with no 3-month CDP, no new T1 Gd+ or CU lesions.
Results: The proportions of patients qualifying relapse free or 3-month CDP free were similar irrespective of CT dose or treatment order. Relapses (median follow-up 122.9 to 123.9 weeks): CP 3.5, 75.6% (68/98); CP 5.25, 75.3% (61/92); CC 7.0, 81.2% (134/186); CC 8.75, 76.7% (132/186) and PC 3.5, 79.6% (180/244); respective proportions without confirmed 3-month CDP (median time on study 121.5 to 124.4 weeks): 81.6% (80/98); 90.2% (83/92); 88.2% (164/186); 83.9% (156/186) and 83.2% (203/244). Proportions with no new T1 Gd+ lesions: CP 3.5, 73.0% (65/98); CP 5.25, 80.2% (65/92); CC 7.0, 88.9% (144/186); CC 8.75, 89.9% (152/186) and PC 3.5, 85.1% (188/244); respective proportions with no CU lesions: 34.4% (32/98); 27.6% (24/92); 37.1% (63/186); 43.7% (76/186) and 40.1% (91/244).
Conclusions: Substantial proportions of patients remained free from disease activity measures in CLARITY EXT, including all subgroups, confirming the durable effect of 2 short annual courses of cladribine tablets, which extended for ≥2 additional years.
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, 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.
Abidemi Adeniji and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Abstract: P636
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Cladribine tablets (CT), given annually for 2 years in short-duration courses in CLARITY, significantly improved clinical (relapses and disability progression) and MRI outcomes, and freedom from disease activity in patients with relapsing multiple sclerosis (RMS) vs placebo (PBO). After a treatment gap (median duration ~41 weeks), the CLARITY Extension (EXT) study compared the safety and efficacy of 2 years" additional CT treatment vs no additional treatment. Analysis of CLARITY EXT may provide insights into the proportions of patients remaining free from various markers of disease activity.
Objective: Separate analyses of proportions of patients free from qualifying relapses, confirmed disability progression (CDP), new T1 Gd+ or combined unique (CU) lesions in CLARITY EXT.
Methods: In CLARITY EXT, patients who received PBO in CLARITY were assigned to CT 3.5mg/kg body weight; those who received CT (3.5 or 5.25mg/kg) were re-randomised 2:1 to CT 3.5mg/kg or PBO, resulting in 5 groups: CP 3.5 (CT 3.5mg/kg in CLARITY/PBO in CLARITY EXT, n=98); CP 5.25 (CT 5.25mg/kg in CLARITY/PBO in CLARITY EXT, n=92); CC 7.0 (CT 3.5mg/kg in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=186); CC 8.75 (CT 5.25mg/kg in CLARITY/ CT 3.5mg/kg CLARITY EXT, n=186); PC 3.5 (PBO in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=244). Results are presented for the proportions of patients qualifying relapse free, with no 3-month CDP, no new T1 Gd+ or CU lesions.
Results: The proportions of patients qualifying relapse free or 3-month CDP free were similar irrespective of CT dose or treatment order. Relapses (median follow-up 122.9 to 123.9 weeks): CP 3.5, 75.6% (68/98); CP 5.25, 75.3% (61/92); CC 7.0, 81.2% (134/186); CC 8.75, 76.7% (132/186) and PC 3.5, 79.6% (180/244); respective proportions without confirmed 3-month CDP (median time on study 121.5 to 124.4 weeks): 81.6% (80/98); 90.2% (83/92); 88.2% (164/186); 83.9% (156/186) and 83.2% (203/244). Proportions with no new T1 Gd+ lesions: CP 3.5, 73.0% (65/98); CP 5.25, 80.2% (65/92); CC 7.0, 88.9% (144/186); CC 8.75, 89.9% (152/186) and PC 3.5, 85.1% (188/244); respective proportions with no CU lesions: 34.4% (32/98); 27.6% (24/92); 37.1% (63/186); 43.7% (76/186) and 40.1% (91/244).
Conclusions: Substantial proportions of patients remained free from disease activity measures in CLARITY EXT, including all subgroups, confirming the durable effect of 2 short annual courses of cladribine tablets, which extended for ≥2 additional years.
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, 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.
Abidemi Adeniji and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.