The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study

Background: Multiple sclerosis (MS) diagnostic criteria have changed since the ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria. Objective: The objective of this paper is to assess the effect of cladribine tablets in patients with a first clinical demyelinating attack fulfilling newer criteria (McDonald 2010) for MS vs CIS. Methods: A post hoc analysis for subgroups of patients retrospectively classified as fulfilling or not fulfilling newer criteria at the first clinical demyelinating attack was conducted. Results: Cladribine tablets 3.5 mg/kg (n=68) reduced the risk of next attack or three-month confirmed Expanded Disability Status Scale (EDSS) worsening by 74% vs placebo (n=72); p=0.0009 in patients meeting newer criteria for MS at baseline. Cladribine tablets 5.25 mg/kg (n=83) reduced the risk of next attack or three-month confirmed EDSS worsening by 37%, but nominal significance was not reached (p=0.14). In patients who were still CIS after applying newer criteria, cladribine tablets 3.5 mg/kg (n=138) reduced the risk of conversion to clinically definite multiple sclerosis (CDMS) by 63% vs placebo (n=134); p=0.0003. Cladribine tablets 5.25 mg/kg (n=121) reduced the risk of conversion by 75% vs placebo (n=134); p<0.0001. Conclusions: Regardless of the criteria used to define CIS or MS, 3.5 mg/kg cladribine tablets are effective in patients with a first clinical demyelinating attack. ClinicalTrials.gov registration: The ORACLE-MS study (NCT00725985).