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Effects of Cladribine Tablets on MRI Outcomes in High Disease Activity (HDA) Patients with Relapsing Multiple Sclerosis (RMS) in the Clarity Study

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Gavin Giovannoni, MBBCh, PhD, FCP (Neurol., SA), FRCP, FRCPath , Queen Mary University London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom
Kottil Rammohan, MD , Ohio State University Hospital, Columbus, OH
Stuart Cook, MD , Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ
Giancarlo Comi, MD , Vita-Salute San Raffaele University, Milan, Italy
Peter Rieckmann, MD , Akademisches Krankenhaus Sozialstiftung Bamberg, Bamberg, Germany
Per Soelberg Soerensen, MD , Department of Neurology, University of Copenhagen, Copenhagen, Denmark
Patrick Vermersch, MD , University of Lille, Lille, France
Fernando Dangond, MD , EMD Serono, Inc., Billerica, MA
Christine Hicking, MS , Merck KGaA, Darmstadt, Germany
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Background: In the CLARITY study, treatment with cladribine tablets (CT) vs. placebo (PBO) showed strong efficacy in a large cohort of patients with RMS over 2 years. Patients with high disease activity (HDA) are at higher risk of relapses and disability progression.

Objectives: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs. PBO on outcomes assessed by magnetic resonance imaging (MRI) in subgroups of CLARITY patients with evidence of HDA at study entry, using two HDA definitions.

Methods: CLARITY patients randomized to CT3.5 or PBO were retrospectively analyzed using two sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1. high relapse activity (HRA), which was defined as ≥2 relapses during the year before study entry whether on DMD treatment or not; 2. HRA plus treatment non-response (HRA+DAT) in which DAT was defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the year before study entry while on therapy with other DMDs.

Results: For cumulative new T1 Gd+ lesions, the relative risk ratio (RRR) in the HRA subgroup (0.087, 95%CI:0.052;0.144) was significantly lower in favor of CT3.5 (n=130) over PBO (n=131, p< 0.0001). In the HRA+DAT subgroup, the RRR (0.077, 95%CI:0.046;0.128) also significantly favored CT3.5 (n=140) vs. PBO (n=149, p< 0.0001). The risk reductions (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097, 95% CI:0.070;0.134, p< 0.0001). For cumulative active T2 lesions, the RRR also significantly favored CT3.5 vs. PBO for HRA (0.263, 95%CI:0.180;0.383, p< 0.0001) and HRA+DAT (0.254, 95% CI:0.178;0.363, p< 0.0001): risk reductions of 74% and 75%, reflecting the 73% reduction in the overall population (0.272, 95%CI:0.221;0.335, p< 0.0001). The RRR for cumulative combined unique active (CUA) lesions significantly favored CT3.5 vs. PBO for HRA (0.212, 95%CI:0.145;0.311, p< 0.0001) and HRA+DAT (0.203, 5%CI:0.141;0.291, p< 0.0001): risk reductions of 79% and 80%, reflecting the 77% overall population reduction (0.234, 95%CI:0.190;0.290, p< 0.0001). Comparable results were seen in the non-HDA counterparts, with no significant treatment-subgroup interactions.

Conclusions: In patients with RMS selected using HDA criteria in the CLARITY study, treatment with CT3.5 produced comparable efficacy in reducing MRI markers of disease activity to the overall study population.

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