Improvements in QoL at 1 year in patients treated with cladribine tablets for highly active relapsing MS: An interim analysis of CLARIFY-MS

Introduction: Multiple sclerosis (MS) is a chronic disabling disease associated with negative effects on quality of life (QoL), including physical and mental health. Objectives: To evaluate the change in QoL for patients with highly active relapsing MS (RMS) at 1 year after initiating treatment with cladribine tablets (CladT). Aims: To assess changes in the physical and mental health composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL- 54) from Baseline to Month 12. Methods: In CLARIFY-MS (NCT03369665), patients with highly active RMS were assigned to receive CladT 3.5 mg/kg cumulative dose over 2 years. Patients were recruited as per the EU label. Results in this interim analysis, conducted prior to the second year of treatment, were assessed using a mixed-effects linear model. Analyses were also conducted for cohorts separated by treatment naive/prior disease-modifying therapy (DMT), and MSQoL reporting performed before/after the start of the COVID- 19 pandemic, as defined as the first reported fatality within each country. Results: Of the 482 patients treated with CladT, 70.1% were female and the mean age was 37.4 years. Of the 426 patients who provided MSQoL-54 data, statistically significant (p<0.0001) improvements from baseline were observed for physical and mental health composite scores with estimated changes of 4.51 (95% confidence interval [CI] 3.24-5.77) and 4.53 (95% CI 3.00-6.05), respectively. Similar trends were apparent for treatment naive (n=121) and prior DMT (n=305) cohorts. There was no indication that the start of the COVID-19 pandemic had an impact on MSQoL-54 reporting. Regarding safety, 322 patients (66.8%) experienced at least one treatmentemergent adverse event, most commonly headache (16%), nasopharyngitis (9%), and lymphopenia (9%). The majority of observed post-baseline lymphopenia events were grade 1-2;fewer patients reported grade 3 lymphopenia, no grade 4 lymphopenia was observed. Conclusions: With only half a therapeutic dose of CladT, this interim analysis demonstrates a statistically significant improvement in the physical and mental health composite scores of MSQoL-54 at 1 year. No new safety concerns were found in this 1-year interim analysis, with no new severe or opportunistic infections that could have an impact on the established benefit:risk profile of CladT in MS.