VANCOUVER—“This exploratory analysis supports the original findings in ORACLE-MS: treatment with two short courses of cladribine tablets significantly delayed conversion to clinically definite multiple sclerosis (MS) in patients with clinically isolated syndrome,” said lead author Mark S. Freedman, HBSc, MSc, MD, at the 68th Annual Meeting of the American Academy of Neurology. In addition, Dr. Freedman and colleagues found that, compared with placebo, cladribine tablets (3.5 mg/kg) significantly reduce the risk of next attack or disability worsening in patients with early relapsing MS, as defined by the McDonald 2010 criteria.
Mark S. Freedman, HBSc, MSc, MD
In 2014, the ORACLE-MS study in patients with a first clinical demyelinating event who were at high risk of converting to MS showed that cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of clinically definite MS, compared with placebo. The ORACLE-MS study recruited patients with early-stage disease by excluding patients who were already considered to have MS according to the McDonald 2005 diagnostic criteria. The revision of the McDonald criteria in 2010 allowed a diagnosis of MS in patients with a single event and evidence of dissemination in time and space from a single MRI scan.
For the present study, Dr. Freedman, who is Professor of Neurology at the University of Ottawa, and colleagues conducted an exploratory analysis of whether cladribine tablets reduced the risk of a second attack or confirmed disability progression in patients who would now be described as having early relapsing MS, according to the McDonald 2010 criteria.
In the ORACLE-MS study cohort, patients were between ages 18 and 55 with a first demyelinating event within 75 days before screening, two or more clinically silent lesions of 3 mm or more on T2-weighted brain MRI scan, and an Expanded Disability Status Scale (EDSS) score of 5 or less. Patients were randomized in equal groups to placebo, cladribine 3.5 mg/kg, or cladribine 5.25 mg/kg. For the present study, baseline MRI scans (excluding the spinal cord) were retrospectively reviewed for MS diagnosis according to the McDonald 2010 criteria.
The exploratory end point in this analysis was time to next attack or EDSS progression in patients who met McDonald 2010 criteria at baseline and in those patients who did not fulfill the revised criteria (ie, those with clinically isolated syndrome).
After applying the McDonald 2010 MS diagnostic criteria, Dr. Freedman and colleagues considered 223 (36.2%) of the 616 participants in ORACLE-MS to have had MS at baseline.
Among these patients, cladribine tablets 3.5 mg/kg significantly reduced the risk of next attack or disability worsening by 74% versus placebo.
In patients who did not meet the McDonald 2010 criteria at baseline, cladribine tablets 3.5 mg/kg also significantly reduced the risk of next attack or disability worsening by 63% versus placebo. Cladribine tablets 5.25 mg/kg also significantly reduced the risk of next attack or disability worsening by 75% versus placebo. This study was sponsored by EMD Serono.
—Glenn S. Williams