Efficacy of Cladribine Tablets 3.5 mg/kg in High Disease Activity (HDA) Subgroups of Patients with Relapsing Multiple Sclerosis (RMS) in the CLARITY Study (P6.360)

Objective: To compare the effects of CT 3.5 mg/kg (CT3.5) vs placebo in subgroups of CLARITY patients selected using two HDA definitions. Background: In the CLARITY study, treatment with cladribine tablets (CT) vs placebo showed strong efficacy in a large cohort of patients with RMS over 2 years. Patients with HDA are at higher risk of relapses and disability progression; post hoc analysis of CLARITY may provide insights into the efficacy of CT in those patients. Design/Methods: CLARITY patients randomized to CT3.5 (N=433) or placebo (N=437) were retrospectively analyzed using two different HDA definitions based on relapse history, prior treatment, and MRI characteristics. Patients were categorized according to whether they had experienced a high relapse rate ([HRR] ≥2 relapses in the previous year) regardless of prior treatment, or a HRR with/without treatment failure ([HRR/TF] ≥2 relapses in the previous year, or ≥1 relapse in previous year while on DMD therapy and ≥1 T1 Gd+ or ≥9 T2 lesions). Results: In the overall CLARITY population, CT3.5 reduced the risk of 6-month confirmed EDSS progression by 47% (HR=0.53, 95%CI:0.36;0.79) vs placebo. A larger risk reduction for CT3.5 vs placebo of 82% was seen (HR=0.18 each, 95%CI:0.08;0.44 and 0.07;0.43) in the HRR subgroup (p=0.0036 nominal significance vs non-HRR) and the HRR/TF subgroup (p=0.0037 nominal significance vs non-HRR/TF), indicating greater responsiveness to CT3.5 in patients identified by these criteria. Similar patterns were observed for time to 3-month EDSS progression. ARR was lower with CT3.5 than placebo in the overall population (RR=0.42, 95%CI:0.33;0.52), and even lower with HRR (RR=0.32, 95%CI:0.22;0.47) and HRR/TF (RR=0.33;95%CI:0.23;0.48), each p Conclusions: In the CLARITY study, patients identified by HDA criteria showed clinical and MRI responses to CT3.5 that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population. Disclosure: Dr. Giovannoni has received personal compensation for activities with AbbVie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex for honoraria. Dr. Giovannoni has received personal compensation from Elsevier in a co-chief editor capacity of MS and Related Disorders. Dr. Giovannoni has received research support from Biogen, Ironwood, Merck Serono, Merz, and Novartis. Dr. Rammohan has received personal compensation for activities with EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme Corporation, Novartis, Teva Neurosciences, Acorda, Bayer Healthcare, Merck Serono, and Roche/Genentech Inc. as a speaker, steering committee member, or consultant. Dr. Rammohan has received research support from Bayer Healthcare. Dr. Cook has received personal compensation for activities with Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc., as a lecturer, consultant, or advisory board member. Prof. Comi has received personal compensation for activities with Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion Sano as a speaker, consultant or participating on an advisory board. Dr. Rieckmann has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Boehringer Ingelheim, Novartis, Merck-Serono, Teva, Teva Pharmaceutical Industries, Sanofi-Aventis, Serono Symposia International Foundation and Genzyme. Dr. Soelberg-Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, Elan, and GlaxoSmithKline, and Bayer. Dr. Soelberg-Sorensen has received personal compensation in an editorial capacity for European Journal of Neurology, Multiple Sclerosis Journal, European Journal of Neurology, and Therapeutic Advances in Neurological Disorders. Dr. Soelberg-Sorensen has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, the Danish Multiple Sclerosis Society, and the Danish Medical Research Council. Dr. Vermersch has received personal compensation for activities with Biogen, Roche, Merck, Teva, Sanofi Genzyme, and Almirall. Dr. Vermersch has received research support from Roche, Biogen and Sanofi Genzyme. Dr. Dangond has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Hicking has received personal compensation for activities with Merck KGaA, Darmstadt, Germany as an employee. Dr. Hicking has received personal compensation for activities with Merck KGaA, Darmstadt, Germany as an employee.