Benefits of Cladribine Tablets on Magnetic Resonance Imaging (MRI) Outcomes in Patients with Multiple Sclerosis: Analysis of Pooled Data from the CLARITY and ONWARD Studies

Background: Treatment with cladribine tablets (CT) in the CLARITY and ONWARD studies demonstrated efficacy vs placebo across a range of patients with active multiple sclerosis (MS). Combining efficacy data from the double-blind periods of these studies enables the assessment of the effects of 2 years' treatment with CT 3.5mg/kg (cumulative dose) on magnetic resonance imaging (MRI) outcomes.

Objectives: To summarize MRI outcomes in patients with relapsing MS (RMS) treated with CT 3.5mg/kg vs placebo, including various subgroups, in pooled data from the CLARITY and ONWARD studies.

Methods: Data from the 2-year, double-blind periods of CLARITY and ONWARD were used to analyse MRI outcomes for CT 3.5mg/kg in all patients with RMS (n=1067), and in subgroups defined by baseline characteristics. Patients from ONWARD on CT or placebo were also taking IFN-beta. Risk of cumulative new T1 Gd+ or active T2 lesions was compared in terms of relative risk ratio (RRR) and 95% confidence intervals (95% CI; from a negative binomial regression model) for patients treated with CT 3.5mg/kg or placebo. Subgroups included patients with no T1 Gd+ lesions (n=759) or with ≥1 T1 Gd+ lesions (n=308); EDSS score ≤3.0 (n=653) or ≥3.5 (n=414). Additional analyses included, among others, subgroups of patients with/without high disease activity; 0 or ≥1 relapse in the prior 12 months; <9 or ≥9 T2 lesions; prior or no prior use of DMDs; males or females, and age ≤40 or >40 years.

Results: Significant reductions in the risk of cumulative new T1 Gd+ lesions were seen in favor of CT 3.5mg/kg vs placebo in the overall population (RRR [95% CI]: 0.10 [0.076-0.140]) and the subgroups: no T1 Gd+ lesions RRR: 0.13 (0.080-0.194), ≥1 T1 Gd+ lesions RRR: 0.09 (0.059-0.133), EDSS ≤3.0 RRR 0.11 (0.073-0.152), EDSS ≥3.5 RRR 0.09 (0.050-0.159). The risk of cumulative active T2 lesions was also significantly reduced overall (RRR: 0.29 [0.232-0.349]) and across patient subgroups: no T1 Gd+ lesions RRR: 0.30 (0.231-0.398), ≥1 T1 Gd+ lesions RRR: 0.24 (0.183-0.322), EDSS ≤3.0 RRR: 0.30 (0.231-0.377). EDSS ≥3.5 RRR: 0.25 (0.176-0.360).

Conclusions: Analysis of pooled CLARITY and ONWARD data showed that CT 3.5mg/kg significantly reduced the cumulative number of new T1 Gd+ and active T2 lesions compared with placebo in a population of patients with active RMS. Significant reductions in new T1 Gd+ and active T2 lesions were also seen with CT 3.5mg/kg vs placebo across a range of patient subgroups.