Benefits of Cladribine Tablets in Patients with Multiple Sclerosis Free from Clinical and Radiological Indicators of Disease Activity in the CLARITY EXTENSION Study

Friday, May 26, 2017: 2:51 PM
R06 (New Orleans Convention Center)
Gavin Giovannoni, MD , Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Stuart Cook, MD , Rutgers, The State University of New Jersey, Newark, NJ
Peter Rieckmann, MD , Akademisches Krankenhaus Sozialstiftung Bamberg, Bamberg, Germany
Kottil Rammohan, MD , Ohio State University Hospital, Columbus, OH
Per Soelberg-Sorensen, MD , Copenhagen University Hospital, Copenhagen, Denmark
Patrick Vermersch, MD , University of Lille, Lille, France
Abidemi Adeniji, PhD , EMD Serono, Inc., Billerica, MA
Fernando Dangond, MD , EMD Serono, Inc., Billerica, MA
Mary Lee, NA , Caudex, New York, NY
Michele Springer, BA , Caudex, New York, NY

Background: Cladribine tablets (CT), given annually for 2 years in short-duration courses in CLARITY, significantly improved clinical (relapses and disability progression) and MRI outcomes, and freedom from disease activity in patients with relapsing multiple sclerosis (RMS) vs placebo (PBO). After a treatment gap (median duration ~41 weeks), the CLARITY Extension (EXT) study compared the safety and efficacy of 2 years' additional CT treatment vs no additional treatment. Analysis of CLARITY EXT may provide insights into the proportions of patients remaining free from various markers of disease activity.

Objectives: Separate analyses of proportions of patients free from qualifying relapses, confirmed disability progression (CDP), new T1 Gd+ or combined unique (CU) lesions in CLARITY EXT.

Methods: In CLARITY EXT, patients who received PBO in CLARITY were assigned to CT 3.5mg/kg body weight; those who received CT (3.5 or 5.25mg/kg) were re-randomized 2:1 to CT 3.5mg/kg or PBO, resulting in 5 groups: CP 3.5 (CT 3.5mg/kg in CLARITY/PBO in CLARITY EXT, n=98); CP 5.25 (CT 5.25mg/kg in CLARITY/PBO in CLARITY EXT, n=92); CC 7.0 (CT 3.5mg/kg in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=186); CC 8.75 (CT 5.25mg/kg in CLARITY/ CT 3.5mg/kg CLARITY EXT, n=186); PC 3.5 (PBO in CLARITY/ CT 3.5mg/kg in CLARITY EXT, n=244). Results are presented for the proportions of patients qualifying relapse free, with no 3-month CDP, no new T1 Gd+ or CU lesions.

Results: The proportions of patients qualifying relapse free or 3-month CDP free were similar irrespective of CT dose or treatment order. Relapses (median follow-up 122.9 to 123.9 weeks): CP 3.5, 75.6% (68/98); CP 5.25, 75.3% (61/92); CC 7.0, 81.2% (134/186); CC 8.75, 76.7% (132/186) and PC 3.5, 79.6% (180/244); respective proportions without confirmed 3-month CDP (median time on study 121.5 to 124.4 weeks): 81.6% (80/98); 90.2% (83/92); 88.2% (164/186); 83.9% (156/186) and 83.2% (203/244). Proportions with no new T1 Gd+ lesions: CP 3.5, 73.0% (65/98); CP 5.25, 80.2% (65/92); CC 7.0, 88.9% (144/186); CC 8.75, 89.9% (152/186) and PC 3.5, 85.1% (188/244); respective proportions with no CU lesions: 34.4% (32/98); 27.6% (24/92); 37.1% (63/186); 43.7% (76/186) and 40.1% (91/244).

Conclusions: Substantial proportions of patients remained free from disease activity measures in CLARITY EXT, including all subgroups, confirming the durable effect of 2 short annual courses of cladribine tablets, which extended for ≥2 additional years.