MAGNIFY-MS Analysis Further Demonstrates Cladribine’s Direct Impact on Central Nervous System in MS

New post-hoc data from the phase 4 MAGNIFY-MS trial (NCT03364036) showed that treatment with cladribine (Mavenclad; EMD Serono) resulted in increased rates of no evidence of disease activity (NEDA) or progression (NEPAD), suggesting a substantial direct impact on central nervous system (CNS) in highly active multiple sclerosis (MS). Other markers of disease progression, axonal loss, and oligoclonal bands further confirmed these findings.¹

Presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 2, in Nashville, Tennessee, MAGNIFY-MS was a study that assessed the sustained efficacy of cladribine tablets at 3.5 mg/kg cumulative dose over a 2-year period, NEDA and no evidence of progression or active disease, otherwise considered NEPAD, were calculated for 270 patients. In year 1 (Y1), NEDA-3 rate was 32.8% (95% CI, 26.9%-39.4%; n = 229) and NEPAD rate was 32.1% (95% CI, 26.3%-38.6%; n = 229). During year 2 (Y2), NEDA-3 rate was 64.1% (95% CI, 57.2%-70.4%; n = 207) and NEPAD rate was 60.2% (95% CI, 53.3%-66.7%; n = 207).

Led by Nicola De Stefano, MD, PhD, a professor of neurology at the department of medicine, surgery, and neuroscience at the University of Siena, Italy, NEDA-3 was defined as an absence of qualifying relapses, 6-month confirmed disability progression, and MRI activity. NEPAD was defined as NEDA with an absence of 20% progression on both the Timed 25-Foot Walk and 9-Hole Peg tests. Both NEDA and NEPAD were calculated for patients with available data in 2 treatment periods: Y1 post baseline to month 12 (M12) and Y2 post M12 to M24 using logistic regression adjusted for age and baseline Expanded Disability Status Scale score.

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An optical coherence tomography (OCT) performed on both eyes to assess for retinal fiber layer, ganglion cell/inner plexiform layer, macular and its sectors revealed no axonal loss while on cladribine. At both M12 and M24, patients treated with the disease-modifying therapy demonstrated substantial and sustained reductions in cerebrospinal fluid neurofilament light, a marker of neuroaxonal damage.

Complete oligoclonal band disappearance was observed for 2 patients (12.5%) from baseline to M12 and 1 patient (8.3%) from baseline to M24. Furthermore, a decrease in oligoclonal band counts were reported for 9 patients (75.0%) from baseline to M24. Notably, at the same time point, investigators observed a decrease for both immunoglobulin and IgM cerebrospinal fluid levels.

A previous analysis of MAGNIFY-MS, presented at the 2024 ACTRIMS Forum, showed that patients on cladribine had a sustained level of cognition through treatment. At 24 months, treatment with the therapy resulted in a sustained improvement in 43% of the 270-patient cohort, as represented by a 4-point change in Symbol Digit Modalities Test. All told, the probability of being stable or experiencing sustained improvement in cognition was more than 95% with an 8-point score change.²

Cladribine has also demonstrated impacts on physical and mental aspects of quality of life. Findings from the CLARIFY-MS study presented at the 2022 ECTRIMS Congress showed that using the Multiple Sclerosis Quality of Life-54 assessment, cladribine-treated patients showed mean changes of 4.86 points (95% CI, 3.18-6.53) in physical composite scores and 4.80 points (95% CI, 3.13-6.46) in mental health composite scores. Both of these were statistically significant (P <.001 changes="" in="" msqol-54="" scores="" were="" consistent="" across="" both="" the="" treatment-na="" and="" treatment-experienced="" subgroups.="" class="text-inherit">3

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REFERENCES
1. De Stefano N, Achiron A, Barkhof F, et al. Effect of cladribine tablets on markers of disease progression, axonal loss, and oligoclonal bands in patients with relapsing multiple sclerosis: results from MAGNIFY-MS. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; Nashville, TN. ABSTRACT DMT01
2. 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.