Benefits of Cladribine Tablets on No Evidence of Disease Activity (NEDA) Status in Patients with Multiple Sclerosis: Analysis of Pooled Data from CLARITY and ONWARD

Background: Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy vs placebo across a spectrum of patients with active multiple sclerosis (MS). Combining efficacy data from the double-blind periods of these studies enables the effects of 2 years' treatment with cladribine tablets (3.5mg/kg cumulative dose) on the proportion of patients with no evidence of disease activity (NEDA) to be assessed.

Objectives: To summarize proportions of patients with no evidence of disease activity in patients with relapsing MS (RMS) treated with cladribine tablets 3.5mg/kg, including various subgroups, in the CLARITY and ONWARD studies. 

Methods: Data from the 2-year, double-blind periods of CLARITY and ONWARD were used to summarize the efficacy of cladribine tablets 3.5mg/kg in patients with RMS (n=1067), and in subgroups defined by baseline characteristics. ONWARD subjects on cladribine or placebo were also taking IFN-beta. Data for patients achieving NEDA (defined as no qualifying relapses, no 3-month confirmed EDSS progression, no new or enhancing T1 Gd+ lesions and no new or active T2 lesions), were compared using odds ratios (OR) and 95% confidence intervals (95% CI) for patients treated with cladribine tablets 3.5mg/kg or placebo. Subgroups analyzed 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 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 disease-modifying drugs; males or females, and age ≤40 or >40 years (not described here).

Results: Cladribine tablets 3.5mg/kg showed consistent benefits vs placebo in the proportion of patients achieving NEDA in the overall population (OR [95% CI]: 3.95 [2.90-5.37]) and in the subgroups: no T1 Gd+ lesions OR: 3.82 (2.71-5.38), ≥1 T1 Gd+ lesions OR: 8.12 (3.31-19.90), EDSS ≤3.0 OR 4.36 (2.90-6.56), EDSS ≥3.5 OR 3.48 (2.17-5.57).

Conclusions: Analysis of pooled data from CLARITY and ONWARD showed that cladribine tablets 3.5mg/kg significantly increased the proportion of patients with no evidence of disease activity compared with placebo in a population of patients with active RMS. Compared with placebo, cladribine tablets also showed significant increases in the proportion of patients with NEDA across a range of patient subgroups.