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

Mark S Freedman, Thomas P Leist, Giancarlo Comi, Bruce Ac Cree, Patricia K Coyle, Hans-Peter Hartung, Patrick Vermersch, Doris Damian, Fernando Dangond, Mark S Freedman, Thomas P Leist, Giancarlo Comi, Bruce Ac Cree, Patricia K Coyle, Hans-Peter Hartung, Patrick Vermersch, Doris Damian, Fernando Dangond

Abstract

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).

Keywords: Cladribine tablets; McDonald 2010 criteria; clinically isolated syndrome; conversion to clinically definite multiple sclerosis; early multiple sclerosis; efficacy.

Figures

Figure 1.
Figure 1.
Kaplan-Meier cumulative incidence curve. Time to next attack or three-month confirmed EDSS worsening in patients retrospectively classified as meeting newer diagnostic criteria for MS at baseline. *Hazard ratio from Cox proportional hazards model with effects for treatment adjusted for the stratification factor (region); p values from two-sided Wald test. CI: confidence interval; EDSS: Expanded Disability Status Scale; HR: hazard ratio; MS: multiple sclerosis.
Figure 2.
Figure 2.
Kaplan-Meier cumulative incidence curve. Time to next attack or three-month confirmed EDSS worsening in patients retrospectively classified as not meeting newer diagnostic criteria for MS at baseline (i.e. newer CIS definition). *Hazard ratio from Cox proportional hazards model with effects for treatment adjusted for the stratification factor (region); p values from two-sided Wald test. CI: confidence interval; CIS: clinically isolated syndrome; EDSS: Expanded Disability Status Scale; HR: hazard ratio; MS: multiple sclerosis.
Figure 3.
Figure 3.
Kaplan-Meier cumulative incidence curve. Time to next evidence of disease activity in patients retrospectively classified as meeting newer diagnostic criteria for MS at baseline. †Next evidence of disease activity based on McDonald 2005 criteria (i.e. attack or any EDSS worsening or MRI event (defined as a new T1 Gd+ or new or enlarging T2 lesions on MRI)). *Hazard ratio from Cox proportional hazards model with effects for treatment adjusted for the stratification factor (region); p values from two-sided Wald test. CI: confidence interval; EDSS: Expanded Disability Status Scale; Gd+: gadolinium enhancing; HR: hazard ratio; MS: multiple sclerosis; MRI: magnetic resonance imaging.
Figure 4.
Figure 4.
Kaplan-Meier cumulative incidence curve. Time to next evidence of disease activity in patients retrospectively classified as not meeting newer diagnostic criteria for MS at baseline (i.e. newer CIS definition). †Next evidence of disease activity based on McDonald 2005 criteria (i.e. attack or any EDSS worsening or MRI event (defined as a new T1 Gd+ or new or enlarging T2 lesions on MRI)). *Hazard ratio from Cox proportional hazards model with effects for treatment adjusted for the stratification factor (region); p values from two-sided Wald test. CI: confidence interval; EDSS: Expanded Disability Status Scale; Gd+: gadolinium enhancing; HR: hazard ratio; MS: multiple sclerosis; MRI: magnetic resonance imaging.

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Source: PubMed

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