Subgroup analysis of clinical and MRI outcomes in participants with a first clinical demyelinating event at risk of multiple sclerosis in the ORACLE-MS study.

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Mult Scler Relat Disord


washington; seattle; swedish neuro


BACKGROUND: In the Phase 3, 96-week ORACLE-MS study, cladribine 10 mg tablets (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years) significantly reduced the rate of conversion to clinically definite multiple sclerosis (CDMS) per the Poser criteria (henceforth referred to as CDMS), multiple sclerosis (MS) per the 2005 McDonald criteria, and the number of new or persisting T1 gadolinium-enhancing (Gd+), new or enlarging T2, and combined unique active (CUA) lesions versus placebo in participants with a first clinical demyelinating event (FCDE). Patient demographic and disease characteristics may be predictors of disease progression. The current study analyzed the effect of cladribine tablets in subgroups of participants in the ORACLE-MS study by baseline demographics and disease characteristics.

METHODS: This analysis retrospectively examined data collected from 616 participants enrolled in the ORACLE-MS study (placebo, n=206; cladribine tablets 3.5 mg/kg, n=206; cladribine tablets 5.25 mg/kg, n=204). Five subgroups were predetermined by baseline demographics, including sex, age (≥30 years), classification of FCDE, and lesion characteristics, including absence or presence of T1 Gd+ lesions and number of T2 lesions (≥9). Selected endpoints of the ORACLE-MS study were re-analyzed for these subgroups. The primary and main secondary endpoints were time to conversion to CDMS and MS (2005 McDonald criteria), respectively. Secondary magnetic resonance imaging (MRI) endpoints included cumulative T1 Gd+ and new or enlarging T2 lesions. Cox proportional hazards models were used to evaluate time to conversion to CDMS and MS (2005 McDonald criteria). This analysis focused primarily on the results for the cladribine tablets 3.5 mg/kg group because this dosage is approved for relapsing forms of MS.

RESULTS: In the overall intent-to-treat (ITT) population, cladribine tablets 3.5 mg/kg significantly reduced the risk of conversion to CDMS (hazard ratio [HR]=0.326; P

CONCLUSION: In this post hoc analysis of the ORACLE-MS study, cladribine tablets reduced the risk of conversion to multiple sclerosis and lesion burden in participants with an FCDE in the overall ITT population and multiple subgroups defined by baseline demographics and lesion characteristics.

Clinical Institute

Neurosciences (Brain & Spine)