Contributions
Abstract: P549
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In the CLARITY study, treatment with Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (MS).
Objective: The effect of CT3.5 on the rate and severity of relapses (using hospitalisation and steroid use as proxy indicators), and the effect of adjusting for covariates was evaluated in post hoc analyses.
Methods: Qualifying relapse was defined by Kurtzke Functional Score status and specified clinical parameters. Qualifying relapse relative risk (RR) was estimated for patients treated with CT3.5 (N=433) and PBO (N=437) at Weeks 24, 48 and 96 by Poisson regression with treatment and various alternating covariates (gender, age, age at time of diagnosis, disease duration, and pre-treatment) as main effects and by adding treatment by covariate interaction effects. All relapses were also analysed; analyses were post hoc and exploratory.
Results: Risk of qualifying relapse was significantly lower for CT3.5 vs PBO at Weeks 24, 48 (both p< 0.001) and Week 96 (Week 96: RR 0.42 [95% confidence interval (CI) 0.34, 0.53]; p< .0001). RR of all relapses (Week 96; CT3.5 vs PBO) was 0.43 [95%CI 0.37, 0.51]; p< .0001. Annualised relapse rates for PBO and CT3.5 were 0.35 and 0.15, (qualifying) and 0.63 and 0.27 (all relapses), respectively. Compared to PBO, the CT3.5 group had a significantly reduced risk of qualifying relapses leading to hospitalisation at all timepoints (Week 96 RR 0.41 [95%CI 0.29, 0.57]; p< .0001) and qualifying relapses leading to steroid treatment (Week 96 RR 0.41 [95%CI 0.32, 0.53]; p< .0001). Risk reduction of all relapses for hospitalisation and steroid use were 63% and 62%, respectively (Week 96). Both age at time of diagnosis (p=0.0011) and prior use of disease modifying drugs (p=0.0002) had a significant effect on qualifying relapse rate by Week 96 when added separately to the model. Gender had a marginal effect (p=0.0783) while disease duration had no effect (p=0.8770). None of the covariates influenced the RR of qualifying relapse for CT3.5 vs PBO at Week 96.
Conclusions: The RR of qualifying relapse (and all relapses) was consistently and significantly lower in the CT3.5 group, vs. PBO, for every timepoint (Weeks 24, 48 and 96), including severe relapses requiring hospitalisation or steroid treatment. After adjusting for covariates, the treatment benefit of CT3.5 vs PBO was not diminished by any of these model adjustments.
Disclosure: The CLARITY study: NCT00213135 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 SS has been a steering committee member of clinical trials and has received travel support and speaker fees from Almirall, Bayer, Biogen, Sanofi, Merck, Novartis, and TEVA. MPS has received consulting fees from Biogen Idec, Merck, Teva, Genzyme, Roche, Novartis, GeNeuro and Medday. NDS has received honoraria and consultation fees from Merck Serono S.A., Teva Pharmaceutical Industries, Novartis Pharma AG, BayerSchering AG, Sanofi-Aventis and Serono Symposia International Foundation. 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. AG is an employee of Ares Trading SA, Aubonne, Switzerland, a division of Merck KGaA, Darmstadt, Germany. BK is an employee of Merck KGaA, Darmstadt, Germany. NA is an employee of Merck KGaA, Darmstadt, Germany.
Abstract: P549
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: In the CLARITY study, treatment with Cladribine Tablets 3.5 mg/kg (CT3.5) showed strong efficacy vs placebo (PBO) over 2 years in patients with relapsing multiple sclerosis (MS).
Objective: The effect of CT3.5 on the rate and severity of relapses (using hospitalisation and steroid use as proxy indicators), and the effect of adjusting for covariates was evaluated in post hoc analyses.
Methods: Qualifying relapse was defined by Kurtzke Functional Score status and specified clinical parameters. Qualifying relapse relative risk (RR) was estimated for patients treated with CT3.5 (N=433) and PBO (N=437) at Weeks 24, 48 and 96 by Poisson regression with treatment and various alternating covariates (gender, age, age at time of diagnosis, disease duration, and pre-treatment) as main effects and by adding treatment by covariate interaction effects. All relapses were also analysed; analyses were post hoc and exploratory.
Results: Risk of qualifying relapse was significantly lower for CT3.5 vs PBO at Weeks 24, 48 (both p< 0.001) and Week 96 (Week 96: RR 0.42 [95% confidence interval (CI) 0.34, 0.53]; p< .0001). RR of all relapses (Week 96; CT3.5 vs PBO) was 0.43 [95%CI 0.37, 0.51]; p< .0001. Annualised relapse rates for PBO and CT3.5 were 0.35 and 0.15, (qualifying) and 0.63 and 0.27 (all relapses), respectively. Compared to PBO, the CT3.5 group had a significantly reduced risk of qualifying relapses leading to hospitalisation at all timepoints (Week 96 RR 0.41 [95%CI 0.29, 0.57]; p< .0001) and qualifying relapses leading to steroid treatment (Week 96 RR 0.41 [95%CI 0.32, 0.53]; p< .0001). Risk reduction of all relapses for hospitalisation and steroid use were 63% and 62%, respectively (Week 96). Both age at time of diagnosis (p=0.0011) and prior use of disease modifying drugs (p=0.0002) had a significant effect on qualifying relapse rate by Week 96 when added separately to the model. Gender had a marginal effect (p=0.0783) while disease duration had no effect (p=0.8770). None of the covariates influenced the RR of qualifying relapse for CT3.5 vs PBO at Week 96.
Conclusions: The RR of qualifying relapse (and all relapses) was consistently and significantly lower in the CT3.5 group, vs. PBO, for every timepoint (Weeks 24, 48 and 96), including severe relapses requiring hospitalisation or steroid treatment. After adjusting for covariates, the treatment benefit of CT3.5 vs PBO was not diminished by any of these model adjustments.
Disclosure: The CLARITY study: NCT00213135 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 SS has been a steering committee member of clinical trials and has received travel support and speaker fees from Almirall, Bayer, Biogen, Sanofi, Merck, Novartis, and TEVA. MPS has received consulting fees from Biogen Idec, Merck, Teva, Genzyme, Roche, Novartis, GeNeuro and Medday. NDS has received honoraria and consultation fees from Merck Serono S.A., Teva Pharmaceutical Industries, Novartis Pharma AG, BayerSchering AG, Sanofi-Aventis and Serono Symposia International Foundation. 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. AG is an employee of Ares Trading SA, Aubonne, Switzerland, a division of Merck KGaA, Darmstadt, Germany. BK is an employee of Merck KGaA, Darmstadt, Germany. NA is an employee of Merck KGaA, Darmstadt, Germany.