Benefits of Cladribine Tablets on Relapse Rates and Disability Progression 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. Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of 2 years' treatment with CT 3.5mg/kg (cumulative dose).

Objectives: To summarize the clinical efficacy of CT 3.5mg/kg vs placebo in patients with relapsing MS (RMS), including various subgroups, using pooled data from CLARITY and ONWARD.

Methods: Data from the 2-year, double-blind periods of CLARITY and ONWARD were used to analyse the efficacy of CT 3.5mg/kg in patients with RMS (n=1067), and in subgroups defined by baseline characteristics. Patients from ONWARD on CT or placebo were also taking IFN-beta. Annualized relapse rates (ARR), 3-month (3-m) and 6-month (6-m) confirmed disability progression (CDP) were compared using relative risk ratios (RRR; from a Poisson regression model), and hazard ratios (HR; from a Cox proportional hazard model) and 95% confidence intervals (95% CI) for patients treated with CT 3.5mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 Gd+ lesions (n=759) or ≥1 T1 Gd+ lesions (n=308); EDSS score ≤3.0 (n=653) or ≥3.5 (n=414).

Results: For ARR, consistent benefits were seen with CT 3.5mg/kg vs placebo in the overall population RRR: 0.43 (0.35-0.52) and the subgroups: no T1 Gd+ lesions, 0.46 (0.36-0.59); ≥1 T1 Gd+ lesions, 0.38 (0.27-0.53); EDSS ≤3.0, 0.40 (0.31-0.53), EDSS ≥3.5, 0.47 (0.34-0.64). Benefits favored CT 3.5mg/kg vs placebo in the overall population for time to 3-mCDP (HR: 0.64 [0.48-0.86]) and 6-mCDP (HR: 0.61 [0.43-0.87]), and in each of these outcomes in a majority of subgroups. For 3-mCDP: no T1 Gd+ lesions HR: 0.59 (0.41-0.85), ≥1 T1 Gd+ lesions HR: 0.75 (0.47-1.19), EDSS ≤3.0 HR: 0.76 (0.51-1.14), EDSS ≥3.5 HR: 0.55 (0.36-0.84). For 6-mCDP: no T1 Gd+ lesions HR: 0.59 (0.38-0.91), ≥1 T1 Gd+ lesions HR: 0.66 (0.37-1.18), EDSS ≤3.0 HR: 0.75 (0.46-1.22), EDSS ≥3.5 HR: 0.51 (0.31-0.85).

Conclusions: Analysis of pooled data from CLARITY and ONWARD showed that CT 3.5mg/kg significantly decreased ARR (by 57%) and reduced the risk for 6-month confirmed disability progression (by 39%) vs placebo in a population of patients with active RMS; these effects were also shown in many subgroups.