DX11
A Post Hoc Analysis of No Evidence of Disease Activity (NEDA) in Patients with Highly Active RMS Who Were Treated with Cladribine Tablets in Clarity

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) showed high efficacy vs. placebo (PBO) over 2 years in a large cohort of patients with RMS. Patients with HDA are at higher risk of clinical or MRI activity and disability progression, and hence less likely to attain NEDA (no relapses, MRI activity or progression).

 

Objectives: In a post hoc analysis, to compare the effects of CT 3.5 mg/kg (CT3.5) vs. PBO on the proportion of patients with NEDA in subgroups of CLARITY patients at higher risk of disease progression than the ITT population, using 2 HDA definitions.

 

Methods: Patients were retrospectively analyzed using 2 sets of HDA criteria based on relapse history, prior treatment, and MRI characteristics: 1 high relapse activity (HRA), defined as ≥2 relapses during the year before study entry whether on DMD treatment or not; 2 HRA plus treatment non-response (HRA+DAT) with DAT defined as ≥1 relapse AND ≥1 T1 Gd+ or ≥9 T2 lesions during the year before study entry while on therapy with other DMDs. Data for patients treated with CT 3.5 or PBO who fulfilled these criteria and achieved NEDA status (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no T1 Gd+ lesions and no active T2 lesions) were compared over the 2-year study using odds ratios (OR) and 95% confidence intervals (95%CI).

 

Results: In each HDA subgroup, the proportion of patients who fulfilled individual NEDA criteria was higher with CT3.5. For example, in the HRA subgroup, 76% of CT3.5-treated patients (n=130) were relapse-free and 84% were T1 Gd+ lesion-free vs. 49% and 31%, respectively, for PBO (n=131). In the HRA+DAT subgroup, 77% were relapse-free and 85% were T1 Gd+ lesion-free with CT 3.5 (n=140) vs. 50% and 32%, respectively for PBO (n=149). Composite NEDA score: 43.2% of the HRA subgroup and 43.7% of the HRA+DAT subgroup in CT3.5-treated patients were disease activity free compared with 8.7%, (OR 8.02, 95%CI: 3.93;16.35, p< 0.0001) and 9.0% (OR 7.82, 95%CI:4.03;15.19, p< 0.0001) respectively, of PBO recipients. These values were significantly more favorable than the non-HDA counterpart subgroup in HRA+DAT patients. In the overall CLARITY population, the composite NEDA score also favored CT3.5 (n=433) over PBO (n=437; OR 4.46, 95%CI:3.18;6.26, p< 0.0001).

 

Conclusions: In a large study of patients with active RMS, treatment with CT3.5 significantly increased the proportion of HDA patients with no evidence of disease activity compared with PBO.

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