Abstracts from the 38th Annual Meeting of the Consortium of Multiple Sclerosis Centers: May 29-June 1, 2024 · Nashville, Tennessee

BACKGROUND:The phase IV MAGNIFY-MS (NCT03364036) study investigated onset of action and sustained efficacy of cladribine tablets (CladT; 3.5-mg/kg cumulative dose over 2 years) in highly active relapsing multiple sclerosis.Exploratory substudies assessed disease activity by optical coherence tomography (OCT) and biomarkers in cerebrospinal fluid (CSF) and blood.OBJECTIVES: Evaluate CladT effect on disease activity in the periphery and biomarkers in the central nervous system.METHODS: All analyses were exploratory.No evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) were calculated for 270 patients.NEDA-3 was defined as an absence of qualifying relapses, 6-month confirmed disability progression, and MRI activity (T1 gadolinium-enhancing [Gd+] or active T2 lesions).NEPAD was defined as NEDA with an absence of 20% progression on both the Timed 25-Foot Walk and 9-Hole Peg tests.NEDA and NEPAD were calculated for patients with available data in 2 treatment periods: year 1 (Y1) post baseline (BL) to month 12 (M12) and Y2 post M12 to M24 using logistic regression adjusting for age and BL Expanded Disability Status Scale score.For OCT (n = 36) and CSF (n = 28) substudies, patients gave additional informed consent.OCT was performed on both eyes using thickness measurements of retinal nerve fiber layer, ganglion cell/inner plexiform layer, macular and its sectors (on Zeiss or Heidelberg Spectralis machines).Changes in CSF were described as a decrease or complete disappearance of oligoclonal bands (OCB) for patients with ≥ 2 OCB at BL, and percentage change from BL for neurofilament light (NfL) and immunoglobulins (Igs).RESULTS: In 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 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).No axonal loss was evident in OCT measures.Substantial (> 50%) and sustained reduction in CSF NfL was observed at M12 and M24.Complete OCB disappearance was observed for 2 patients (12.5%) from BL to M12 and 1 patient (8.3%) from BL to M24; a decrease in OCB counts was reported for 9 patients (75.0%) from BL to M24.A decrease for both IgG and IgM CSF levels was recorded at M24. CONCLUSIONS: These results may suggest a direct effect of CladT within the CNS.NEDA-3 and NEPAD data provide evidence for a substantial impact of CladT on disease activity and progression.