DX34
Cladribine Tablets in the ORACLE-MS Study Open-Label Maintenance Period: Analysis of Efficacy in Patients After Conversion to Clinically Definite Multiple Sclerosis (CDMS)

Thursday, May 25, 2017
B2 (New Orleans Convention Center)
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Thomas Leist, MD , Thomas Jefferson University, Philadelphia, PA
Mark S Freedman, MD , University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
Bruce AC Cree, MD, PhD , Neurology, University of California, San Francisco, CA
Patricia K Coyle, MD , Stony Brook University, Stony Brook, NY
Hans-Peter Hartung, MD , Department of Neurology, Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany
Patrick Vermersch, MD , University of Lille, Lille, France
Doris Damian, 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
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Background: The CLARITY study in patients with active MS showed that annualized relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for 2 years in short-duration courses, vs placebo. The efficacy observed in CLARITY was maintained without further active treatment during CLARITY Extension. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS (CDMS) compared with placebo. If CDMS occurred in the double-blinded, initial treatment period (ITP), patients were treated with subcutaneous (sc) interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week in an open-label maintenance period (OLMP).

Objectives: To assess the annualized relapse rate (ARR) during ORACLE-MS OLMP, in patients randomized to 3.5 mg/kg and 5.25 mg/kg, or placebo, in the ITP.

Methods: Participation in the ORACLE-MS OLMP was dependent upon the clinical course of the patient's disease in the ITP. Patients in ORACLE-MS who converted to CDMS (according to Poser criteria) during the ITP entered the OLMP, and were treated with subcutaneous interferon-beta 1a (titrated over 4 weeks up to the dose of 44 mcg) administered 3 times per week.

Results: 109 patients in ORACLE-MS converted to CDMS in ITP and received at least one dose of interferon-beta 1a. The median time on interferon-beta 1a was 56.0 weeks. Estimated annualized relapse rates (ARR) in the OLMP were 0.14 (95% confidence interval [CI] 0.00-0.27) for patients (n=25) originally treated with cladribine 3.5 mg/kg; 0.24 (95% CI 0.07-0.40) for patients (n=24) originally treated with 5.25 mg/kg and 0.42 (95% CI 0.28-0.56) for patients (n=60) who originally received placebo in the ITP.

Conclusions: A significant treatment effect versus placebo of cladribine tablets given in ITP continues to be observed in patients who convert to CDMS and switch to treatment with a different disease modifying drug (sc interferon beta-1a). Patients who had been treated with cladribine tablets and who had converted to MS during ORACLE-MS ITP had lower ARR during the OLMP, relative to those patients who had received placebo during ORACLE-MS ITP. Durable efficacy of cladribine tablets in ORACLE-MS into the OLMP is consistent with results of the CLARITY and CLARITY Extension studies.

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