Abstract: P894
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In the CLARITY study, Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (RMS). No Evidence of Disease Activity-3 (NEDA-3) status was achieved in significantly more patients receiving CT3.5 than those receiving PBO (47% and 17%, respectively p< 0.0001). Efficacy in patients receiving CT3.5 in CLARITY was maintained in Years 3 and 4 when patients were randomised to PBO in CLARITY Ext after a variable bridging interval of up to 116 weeks duration when patients were not treated with Cladribine Tablets.
Objective: Post hoc analysis to determine NEDA-3 status in patients who received CT3.5 in CLARITY and who were then treated with PBO (CP3.5) or CT3.5 (CC7) in CLARITY Ext.
Methods: Patients were retrospectively analysed for NEDA-3 status (patients with no relapse, no 6-month Expanded Disability Status Scale (EDSS) progression and no T1 gadolinium-enhancing or active T2 lesions) in the first year of CLARITY Ext for the CP3.5 and CC7 groups; N=98 and N=186, respectively. Variable bridging interval from the core and Ext studies was used as a proxy to determine NEDA in a 12-month observation up to the end of Year 4 (Y4, bridging ≤43 weeks; CP3.5 group; N=54, CC7 group; N=98 with confirmed NEDA status) or up to the end of Year 5 (Y5, bridging >43 weeks; CP3.5 group; N=40, CC7 group; N=77 with confirmed NEDA status). Differences in NEDA-3 in the CP3.5 and CC7 group were analysed by logistic regression with duration of study bridging included as a fixed effect.
Results: In 12 months up to the end of Year 4, annual NEDA-3 was achieved in 46% (25/54) of patients in the CP3.5 group and 48% (47/98) in the CC7 group. Up to the end of Years 5 after commencing CLARITY, annual NEDA-3 was observed in 35% (14/40) of the CP3.5 group and 48% (37/77) of the CC7 group. Adjusting for the length of the bridging interval, there was no significant difference between annual NEDA-3 in the CP3.5 (41.5%, 95% CI 32.4-60.0%) and CC7 (48.0%, 95% CI 40.2-64.4%) groups p=0.31). The duration of bridging interval was not a significant variable (p=0.38). Similar patterns were observed when proportions of patients' annual relapse-free and annual 6-month EDSS progression free were examined.
Conclusions: In this post hoc analysis, following treatment with CT3.5 in Years 1 and 2, annual NEDA‑3 status was sustained in patients treated with either CT3.5 or PBO in CLARITY Ext up to the end of Year 5.
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: 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. 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: P894
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In the CLARITY study, Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (RMS). No Evidence of Disease Activity-3 (NEDA-3) status was achieved in significantly more patients receiving CT3.5 than those receiving PBO (47% and 17%, respectively p< 0.0001). Efficacy in patients receiving CT3.5 in CLARITY was maintained in Years 3 and 4 when patients were randomised to PBO in CLARITY Ext after a variable bridging interval of up to 116 weeks duration when patients were not treated with Cladribine Tablets.
Objective: Post hoc analysis to determine NEDA-3 status in patients who received CT3.5 in CLARITY and who were then treated with PBO (CP3.5) or CT3.5 (CC7) in CLARITY Ext.
Methods: Patients were retrospectively analysed for NEDA-3 status (patients with no relapse, no 6-month Expanded Disability Status Scale (EDSS) progression and no T1 gadolinium-enhancing or active T2 lesions) in the first year of CLARITY Ext for the CP3.5 and CC7 groups; N=98 and N=186, respectively. Variable bridging interval from the core and Ext studies was used as a proxy to determine NEDA in a 12-month observation up to the end of Year 4 (Y4, bridging ≤43 weeks; CP3.5 group; N=54, CC7 group; N=98 with confirmed NEDA status) or up to the end of Year 5 (Y5, bridging >43 weeks; CP3.5 group; N=40, CC7 group; N=77 with confirmed NEDA status). Differences in NEDA-3 in the CP3.5 and CC7 group were analysed by logistic regression with duration of study bridging included as a fixed effect.
Results: In 12 months up to the end of Year 4, annual NEDA-3 was achieved in 46% (25/54) of patients in the CP3.5 group and 48% (47/98) in the CC7 group. Up to the end of Years 5 after commencing CLARITY, annual NEDA-3 was observed in 35% (14/40) of the CP3.5 group and 48% (37/77) of the CC7 group. Adjusting for the length of the bridging interval, there was no significant difference between annual NEDA-3 in the CP3.5 (41.5%, 95% CI 32.4-60.0%) and CC7 (48.0%, 95% CI 40.2-64.4%) groups p=0.31). The duration of bridging interval was not a significant variable (p=0.38). Similar patterns were observed when proportions of patients' annual relapse-free and annual 6-month EDSS progression free were examined.
Conclusions: In this post hoc analysis, following treatment with CT3.5 in Years 1 and 2, annual NEDA‑3 status was sustained in patients treated with either CT3.5 or PBO in CLARITY Ext up to the end of Year 5.
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: 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. BK is an employee of Merck KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd., a division of Merck KGaA, Darmstadt, Germany.