Background

CLARITY, CLARITY Extension, and ORACLE-MS have previously demonstrated the efficacy of cladribine tablets (CT; cumulative dose 3.5 mg/kg over 2 years). CLASSIC-MS (NCT03961204) seeks to explore the long-term efficacy and durability of effect of CT beyond the 2 annual treatment cycles in patients (pts) enrolled to these parent trials, with the aim of informing future treatment approaches.

Objectives

To present interim data on long-term efficacy and durability of effect of CT and real-world treatment patterns in CLASSIC-MS.

Methods

CLASSIC-MS is an exploratory, low-interventional, multicenter, ambispective, Phase IV study of pts with multiple sclerosis (MS), or those with a first clinical demyelinating event, previously enrolled into Phase III parent trials, and who had received ≥1 course of CT or placebo. The primary objective is long-term mobility (no wheelchair use/bedridden; EDSS <7 in the 3 months prior to first visit in CLASSIC-MS). The main secondary objective is long-term disability status (EDSS <6 any time since last parent study dose [LPSD]). Further objectives seek to assess differences in clinical and magnetic resonance imaging characteristics in long-term responders vs non-responders, with long-term responder status defined as: (A) not requiring further disease-modifying drug (DMD) treatment until ≥4 years after LPSD, or (B) no evidence of disease reactivation based on clinical outcomes in the 4 years following LPSD. Analyses are descriptive.

Results

The interim population comprised 147 pts (61% female; 88% exposed to CT in parent studies; mean EDSS 3.3±2.1 at baseline of CLASSIC-MS [vs. 2.6±1.2 at baseline of parent studies]). Median time since LPSD was 10 (range 8–14) years. The proportion of pts not using a wheelchair/bedridden in the 3 months prior to CLASSIC-MS was 94.6% (139/147) and the proportion of pts with no need of ambulatory device at any time since LPSD was 83.7% (EDSS <6; 123/147). Overall, 73.5% of pts (108/147) were long-term responders by definition A and 45.6% by definition B. In addition, 63.3% of pts (93/147) received no subsequent DMD treatment after LPSD, and 59.1% of pts maintained active employment.

Conclusions

Interim data from CLASSIC-MS, with a median of 10 years’ follow-up, suggests sustained efficacy of CT following 2 annual treatment cycles, with a substantial proportion of pts requiring no further treatment with DMDs or assistive ambulatory device.

CLARITY: NCT00213135; CLARITY Extension: NCT00641537; ORACLE: NCT00725985

Funding: This study was sponsored by Merck KGaA, Darmstadt, Germany.