Contributions
Abstract: P892
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In CLARITY, patients with high disease activity (HDA) relapsing multiple sclerosis had clinical and magnetic resonance imaging responses to Cladribine Tablets 3.5 mg/kg (CT3.5) that were generally better than, or comparable to, the overall CLARITY population.
Objectives: Post hoc analyses to determine the rate of lymphopenia in patients with HDA in the CLARITY/CLARITY Ext CT3.5 cohort.
Methods: Patients were retrospectively analysed using 2 sets of HDA criteria: 1. High relapse activity (HRA), defined as ≥2 relapses in the year before study entry whether on disease modifying drug (DMD) treatment or not 2. HRA + disease activity on treatment (DAT) defined as ≥1 relapse AND ≥1 T1 gadolinium‑enhancing or ≥9 T2 lesions in the year before study entry while on therapy with other DMDs. Patients exposed to CT3.5 in Years 1 and 2 only were the CT3.5 group, patients who received further courses of CT in Years 3 and 4 were the CT7.0 group. The Adverse Event of Special Interest (AESI) lymphopenia was determined based on absolute lymphocyte count (ALC) and lymphopenia analysed across CLARITY and CLARITY Ext.
Results: In CT3.5 at Year 2 (CT3.5-Y2), AESIs/100 patient-years were similar in the HRA (N=196) and HRA+DAT (N=219) subgroups (11.50 and 13.09 respectively) and similar between corresponding non-HDA groups (14.08 [N=489] and 13.46 [N=466]). In CT7.0 at Year 4 (CT7.0-Y4) rates were approximately double to CT3.5-Y2. Mean ALC nadir (x109/L) for CT3.5-Y2 HRA and HRA+DAT were 0.73 and 0.72 respectively; mean nadirs were 0.69 in both corresponding non-HDA subgroups. A similar pattern was seen in CT7.0-Y4, but with lower nadirs than CT3.5-Y2. There were small differences in time to ALC nadir between HDA subgroups. Time to nadir was shorter in CT7.0-Y4 than CT3.5-Y2. For the CT3.5-Y2 group, incidence of Grade 3 lymphopenia was similar between the HDA and corresponding non‑HDA subgroups. In CT7.0-Y4, Grade 3 lymphopenia incidence was lower in the HDA than the non-HDA subgroups. Overall, Grade 3 lymphopenia incidence was lower in CT3.5‑Y2 than CT7.0-Y4. Grade 4 lymphopenia incidence was low in all HDA and non-HDA subgroups.
Conclusions: There were no relevant differences between HDA and non-HDA groups in regard to incidence of the AESI lymphopenia, ALC nadir, and time to ALC nadir. Disease activity at baseline appeared unrelated to the incidence of lymphopenia during CLARITY/CLARITY Ext.
Disclosure: The CLARITY study: NCT00213135; The CLARITY Extension study: NCT00641537 Disclosures: 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). Author disclosures: SC has received honoraria for lectures/consultations from Merck, 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. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, 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. 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. PSS 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. BK is an employee of Merck KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd., a division of Merck KGaA, Darmstadt, Germany.
Abstract: P892
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In CLARITY, patients with high disease activity (HDA) relapsing multiple sclerosis had clinical and magnetic resonance imaging responses to Cladribine Tablets 3.5 mg/kg (CT3.5) that were generally better than, or comparable to, the overall CLARITY population.
Objectives: Post hoc analyses to determine the rate of lymphopenia in patients with HDA in the CLARITY/CLARITY Ext CT3.5 cohort.
Methods: Patients were retrospectively analysed using 2 sets of HDA criteria: 1. High relapse activity (HRA), defined as ≥2 relapses in the year before study entry whether on disease modifying drug (DMD) treatment or not 2. HRA + disease activity on treatment (DAT) defined as ≥1 relapse AND ≥1 T1 gadolinium‑enhancing or ≥9 T2 lesions in the year before study entry while on therapy with other DMDs. Patients exposed to CT3.5 in Years 1 and 2 only were the CT3.5 group, patients who received further courses of CT in Years 3 and 4 were the CT7.0 group. The Adverse Event of Special Interest (AESI) lymphopenia was determined based on absolute lymphocyte count (ALC) and lymphopenia analysed across CLARITY and CLARITY Ext.
Results: In CT3.5 at Year 2 (CT3.5-Y2), AESIs/100 patient-years were similar in the HRA (N=196) and HRA+DAT (N=219) subgroups (11.50 and 13.09 respectively) and similar between corresponding non-HDA groups (14.08 [N=489] and 13.46 [N=466]). In CT7.0 at Year 4 (CT7.0-Y4) rates were approximately double to CT3.5-Y2. Mean ALC nadir (x109/L) for CT3.5-Y2 HRA and HRA+DAT were 0.73 and 0.72 respectively; mean nadirs were 0.69 in both corresponding non-HDA subgroups. A similar pattern was seen in CT7.0-Y4, but with lower nadirs than CT3.5-Y2. There were small differences in time to ALC nadir between HDA subgroups. Time to nadir was shorter in CT7.0-Y4 than CT3.5-Y2. For the CT3.5-Y2 group, incidence of Grade 3 lymphopenia was similar between the HDA and corresponding non‑HDA subgroups. In CT7.0-Y4, Grade 3 lymphopenia incidence was lower in the HDA than the non-HDA subgroups. Overall, Grade 3 lymphopenia incidence was lower in CT3.5‑Y2 than CT7.0-Y4. Grade 4 lymphopenia incidence was low in all HDA and non-HDA subgroups.
Conclusions: There were no relevant differences between HDA and non-HDA groups in regard to incidence of the AESI lymphopenia, ALC nadir, and time to ALC nadir. Disease activity at baseline appeared unrelated to the incidence of lymphopenia during CLARITY/CLARITY Ext.
Disclosure: The CLARITY study: NCT00213135; The CLARITY Extension study: NCT00641537 Disclosures: 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). Author disclosures: SC has received honoraria for lectures/consultations from Merck, 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. GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, 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. 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. PSS 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. BK is an employee of Merck KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd., a division of Merck KGaA, Darmstadt, Germany.