Long-Term Efficacy for Patients Receiving Cladribine Tablets (3.5 mg/kg Over 2 years) in Clarity/Clarity Extension: A Post Hoc Analysis of Classic-MS

Background: CLASSIC-MS (NCT03961204) was a Phase IV study evaluating the long-term efficacy of cladribine tablets (CladT) in patients with relapsing multiple sclerosis who were originally enrolled in the Phase III studies: CLARITY/CLARITY Extension.

Objectives: Post hoc analysis reporting long-term mobility and disability beyond the treatment courses received in CLARITY/CLARITY Extension for patients receiving CladT 3.5 mg/kg cumulative dose over 2 years.

Methods: This post hoc analysis focuses on the sub-group of patients who received the 3.5 mg/kg dose of CladT, compared to placebo. The primary objective was to evaluate long-term mobility (no wheelchair use in the 3 months prior to first visit in CLASSIC-MS and not bedridden at any time since last parent study dose [LPSD], i.e. Expanded Disability Status Scale [EDSS] score <7). The main secondary objective was long-term disability status (no use of an ambulatory device [EDSS <6] any time since LPSD). Data on relapses and subsequent disease-modifying therapy (DMT) use were also collected.

Results: Of the 201 patients included in this analysis, 160 patients received the 3.5 mg/kg dose of CladT (64.4% female; mean[±SD] EDSS: 2.74±1.31 at baseline, 3.78±2.07 at Study Visit 1), and 41 patients were never exposed to CladT (75.6% female; mean EDSS: 2.74±1.33 at baseline, 4.50±2.59 at Study Visit 1). At CLASSIC-MS baseline, time since LPSD was 9.5–14.5 years. The proportion of patients not using a wheelchair in the 3 months prior to Study Visit 1 and not bedridden at any time since LPSD was 88.2% of those in the 3.5 mg/kg group and 77.8% of those never exposed (odds ratio=0.47; 95% confidence interval: 0.186–1.188). Patients who did not use an ambulatory device accounted for 78.8% of patients in the 3.5 mg/kg group, and 75.6% of those never exposed. The proportion of patients remaining relapse-free since LPSD was 46.9% in the 3.5 mg/kg group and 26.8% in the never exposed group. Subsequent DMTs were used by 41.9% of patients in the 3.5 mg/kg group and 73.2% of patients never exposed. Time to subsequent DMT use was 3.9 years in patients in the 3.5 mg/kg group and 1.0 year in those never exposed, at the 25^th percentile.

Conclusions: Numerically, results indicate improved mobility and disability outcomes for patients in the CladT 3.5 mg/kg dose group, with fewer patients using subsequent DMTs during the follow-up period, compared to those never exposed.

Funding: The study was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). Medical writing support was provided by Ruth Butler-Ryan of inScience Communications, Springer Healthcare Ltd, UK, and was funded by the healthcare business of Merck KGaA, Darmstadt, Germany.