Cognitive Resilience and Improvements in Health-Related Quality of Life Over 4 Years in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results from the CLARIFY-MS Extension Study

Background The initial 2-year phase 4 CLARIFY-MS Parent study demonstrated improvements in health-related quality of life (HRQoL) and preserved cognitive function in cladribine tablets (CladT)-treated people with highly active relapsing multiple sclerosis (RMS). Objectives To report 4-year data on cognitive function, HRQoL, other efficacy and safety outcomes from CLARIFY-MS Extension. Methods No additional CladT treatment was protocolled during Extension (as per approved EU label). The primary endpoint was the proportion of participants with no or minimal decline in cognitive function at Month (M) 48 after initial dose versus Parent study baseline. HRQoL, and other efficacy and safety outcomes of CladT were also assessed. Results Overall, 68.6% of the participants (n = 192/280) showed no or minimal decline in cognitive function at M48 versus Parent study baseline. Significant improvements in Multiple Sclerosis Quality of Life-54 scores were observed over 48 months. The beneficial effect of CladT on relapses, radiological activity and disability progression observed in the Parent study were sustained during Extension. No unexpected safety signals were detected. Conclusions CLARIFY-MS Extension demonstrated sustained benefits of CladT on cognitive function and HRQoL in people with highly active RMS for ≤4 years after the initial dose. The 4-year follow-up of the BICAMS battery indicated resilience across different aspects of cognition with CladT. The durable and multidimensional effects of CladT on key efficacy outcomes observed during the 2-year treatment-period of the Parent study were confirmed over the treatment-free Years 3–4 of Extension. The existing safety profile of CladT was confirmed over 4 years.