Individual and Group Level Cognitive Benefits of Cladribine Displayed in MAGNIFY-MS Study

Author(s):

Using a 4-point score change on Symbol Digits Modalities Test, more than 80% of patients had either sustained improvement or no sustained change after 2 years of treatment with cladribine.

Patrick Vermersch, MD, PhD

Two-year data from the MAGNIFY-MS study (NCT03364036) assessing cladribine (Mavenclad; EMD Serono) in patients with highly active relapsing multiple sclerosis (MS) showed a sustained level of cognition in most patients on the agent. Cognitive benefit was evident following the first treatment course, and became more pronounced by month 18 when patients had received the full treatment course.¹

In this analysis, at 24 months, treatment with 3.5 mg/kg of cladribine tablets resulted in sustained improvement in 43% of the 270-patient cohort, as represented by a 4-point change in Symbol Digit Modalities Test (SDMT). Presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 29 to March 2, in West Palm Beach, Florida, the probability of being stable or experiencing sustained improvement in cognition was more than 95% with an 8-point score change.

Lead author Patrick Vermersch, MD, PhD, vice president for research in biology and health at the University of Lille, France, and colleagues, assessed cognitive processing speeds of patients at an individual (4- and 8-point score change) and group levels. On an individual level, time to first sustained improvement (SDMT score changes ≥4 or ≥8) or time to first worsening (SDMT score changes ≤-4 or ≤-8) were measured at months 6, 12, 18, and 24 after treatment initiation and analyzed using the Kaplan-Meier method. In the represented sample, 67% of patients were female, 61% had high-relapse activity, and 43% were treatment naïve.

At the 24-month time point, 45% of patients demonstrated no sustained change and 12% demonstrated sustained worsening on a 4-point score change. Using the 8-point score change, the rate of sustained improvement was estimated at 22%, no sustained change at 74%, and sustained worsening of 4%. Investigators also observed no subgroup differences in outcomes based on prior treatment use or relapse activity severity.

Using a mixed models for repeated measures, group level findings showed improvements in cognition, as demonstrated by SDMT scores, at 6 months (estimated least square [LS] mean increase, 2.05 points; 95% CI, 1.24-2.86). These improvements continued to be detected at months 12, 18, and 24, as demonstrated by increases in scores of 2.54 (95% CI, 1.47-3.62), 4.04 (95% CI, 3.06-5.02), and 3.40 (95% CI, 2.19-4.61) points, respectively (all P <.0001).

Authors noted that the study was limited by the fact that it was single-arm and open-label, so results may be taken with caution. Practice effects were mitigated with the use of alternate forms and with 6 months between each assessment.

At the 2022 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, findings from the CLARIFY-MS study highlighted the physical and mental aspects of quality of life improved through cladribine. Using the Multiple Sclerosis Quality of Life-54 (MSQol-54), physical composite scores were changed by a mean of 4.86 points (95% CI, 3.18-6.53) and mental health composite scores were changed by 4.80 points (95% CI, 3.13-6.46), at the 24-month time point, both of which were statistically significant (P <.0001). Changes in MSQol-54 scores were consistent across both the treatment-naïve and treatment-experienced subgroups.

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REFERENCES
1. Vermersch P, Wiendl H, Barkhof F, et al. Improved cognitive processing speed in patients treated with cladribine tablets for multiple sclerosis: MAGNIFY-MS 2-year findings. Presented at: ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, FL. POSTER P070.
3. Solari A, Montalban X, Lechner-Scott J, et al. Improvements in quality of life over 2 years in patients treated with cladribine tablets for highly active relapsing multiple sclerosis: Final analysis of CLARIFY-MS. Presented at: ECTRIMS Congress; October 26-28, 2022; Amsterdam, Netherlands. P108.