Abstract: 70
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The CLARITY study in patients with active MS showed that annualised relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for 2 years in short-duration courses, vs placebo. The efficacy observed in CLARITY was maintained without further active treatment during CLARITY Extension. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS (CDMS) compared with placebo. If CDMS occurred in the double-blinded, initial treatment period (ITP), patients were treated with subcutaneous (sc) interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week in an open-label maintenance period (OLMP).
Objective: To assess the annualised relapse rate (ARR) during ORACLE-MS OLMP, in patients randomised to 3.5 mg/kg and 5.25 mg/kg, or placebo, in the ITP.
Methods: Participation in the ORACLE-MS OLMP was dependent upon the clinical course of the patient"s disease in the ITP. Patients in ORACLE-MS who converted to CDMS (according to Poser criteria) during the ITP entered the OLMP, and were treated with subcutaneous interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week.
Results: 109 patients in ORACLE-MS converted to CDMS in ITP and received at least one dose of interferon-beta 1a. The median time on interferon-beta 1a was 56.0 weeks. Estimated annualised relapse rates (ARR) in the OLMP were 0.14 (95% confidence interval [CI] 0.00-0.27) for patients (n=25) originally treated with cladribine 3.5 mg/kg; 0.24 (95% CI 0.07-0.40) for patients (n=24) originally treated with 5.25 mg/kg and 0.42 (95% CI 0.28-0.56) for patients (n=60) who originally received placebo in the ITP.
Conclusions: A significant treatment effect versus placebo of cladribine tablets given in ITP continues to be observed in patients who convert to CDMS and switch to treatment with a different disease modifying drug (sc interferon beta-1a). Patients who had been treated with cladribine tablets and who had converted to MS during ORACLE-MS ITP had lower ARR during the OLMP, relative to those patients who had received placebo during ORACLE-MS ITP. Durable efficacy of cladribine tablets in ORACLE-MS into the OLMP is consistent with results of the CLARITY and CLARITY Extension studies.
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).
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.
Thomas Leist is a consultant to EMD Serono, Teva Neuroscience, Biogen, Bayer, Pfizer; and is involved in clinical trials sponsored by EMD Serono, Teva Neuroscience, Bayer, ONO, Novartis, Daiichi, Acorda.
Mark S. Freedman has received compensation from Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva Canada Innovation.
Bruce Cree has served as an advisor or consultant for: AbbVie Inc., Biogen Inc., EMD Serono, Inc., Genzyme Corporation, MedImmune Inc., Novartis Pharmaceuticals Corporation, Shire and Teva Neuroscience, Inc.
Patricia K. Coyle has served as an advisor or consultant for: AbbVie Inc., Accordant, Acorda Therapeutics, Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Inc., Genentech/Roche, Genzyme/Sanofi, Novartis Pharmaceuticals Corporation, Teva Pharmaceuticals USA, and received grants for clinical research from: Actelion Pharmaceuticals, Ltd., Biogen, Genentech/Roche, Novartis Pharmaceuticals Corporation and Opexa Therapeutics, Inc.
Hans-Peter Hartung has received honoraria for consulting, membership of steering committees and advisory boards, and speaking at symposia - with approval of the Rector of Heinrich-Heine-University - from Bayer Healthcare, Biogen Idec, Genzyme, Medimmune, Merck Serono, Novartis Pharma AG, Teva, Sanofi-Aventis, Receptos and Roche.
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.
Doris Damian and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Abstract: 70
Type: Oral
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The CLARITY study in patients with active MS showed that annualised relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for 2 years in short-duration courses, vs placebo. The efficacy observed in CLARITY was maintained without further active treatment during CLARITY Extension. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS (CDMS) compared with placebo. If CDMS occurred in the double-blinded, initial treatment period (ITP), patients were treated with subcutaneous (sc) interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week in an open-label maintenance period (OLMP).
Objective: To assess the annualised relapse rate (ARR) during ORACLE-MS OLMP, in patients randomised to 3.5 mg/kg and 5.25 mg/kg, or placebo, in the ITP.
Methods: Participation in the ORACLE-MS OLMP was dependent upon the clinical course of the patient"s disease in the ITP. Patients in ORACLE-MS who converted to CDMS (according to Poser criteria) during the ITP entered the OLMP, and were treated with subcutaneous interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week.
Results: 109 patients in ORACLE-MS converted to CDMS in ITP and received at least one dose of interferon-beta 1a. The median time on interferon-beta 1a was 56.0 weeks. Estimated annualised relapse rates (ARR) in the OLMP were 0.14 (95% confidence interval [CI] 0.00-0.27) for patients (n=25) originally treated with cladribine 3.5 mg/kg; 0.24 (95% CI 0.07-0.40) for patients (n=24) originally treated with 5.25 mg/kg and 0.42 (95% CI 0.28-0.56) for patients (n=60) who originally received placebo in the ITP.
Conclusions: A significant treatment effect versus placebo of cladribine tablets given in ITP continues to be observed in patients who convert to CDMS and switch to treatment with a different disease modifying drug (sc interferon beta-1a). Patients who had been treated with cladribine tablets and who had converted to MS during ORACLE-MS ITP had lower ARR during the OLMP, relative to those patients who had received placebo during ORACLE-MS ITP. Durable efficacy of cladribine tablets in ORACLE-MS into the OLMP is consistent with results of the CLARITY and CLARITY Extension studies.
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).
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.
Thomas Leist is a consultant to EMD Serono, Teva Neuroscience, Biogen, Bayer, Pfizer; and is involved in clinical trials sponsored by EMD Serono, Teva Neuroscience, Bayer, ONO, Novartis, Daiichi, Acorda.
Mark S. Freedman has received compensation from Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva Canada Innovation.
Bruce Cree has served as an advisor or consultant for: AbbVie Inc., Biogen Inc., EMD Serono, Inc., Genzyme Corporation, MedImmune Inc., Novartis Pharmaceuticals Corporation, Shire and Teva Neuroscience, Inc.
Patricia K. Coyle has served as an advisor or consultant for: AbbVie Inc., Accordant, Acorda Therapeutics, Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Inc., Genentech/Roche, Genzyme/Sanofi, Novartis Pharmaceuticals Corporation, Teva Pharmaceuticals USA, and received grants for clinical research from: Actelion Pharmaceuticals, Ltd., Biogen, Genentech/Roche, Novartis Pharmaceuticals Corporation and Opexa Therapeutics, Inc.
Hans-Peter Hartung has received honoraria for consulting, membership of steering committees and advisory boards, and speaking at symposia - with approval of the Rector of Heinrich-Heine-University - from Bayer Healthcare, Biogen Idec, Genzyme, Medimmune, Merck Serono, Novartis Pharma AG, Teva, Sanofi-Aventis, Receptos and Roche.
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.
Doris Damian and Fernando Dangond are employees of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.