Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting

Abstract

Serum neurofilament light chain (sNfL) is an intensely investigated biomarker in multiple sclerosis (MS). The aim of this study was to explore the impact of cladribine (CLAD) on sNfL and the potential of sNfL as a predictor of long-term treatment response. Data were gathered from a prospective, real-world CLAD cohort. We measured sNfL at baseline (BL-sNfL) and 12 months (12Mo-sNfL) after CLAD start by SIMOA. Clinical and radiological assessments determined fulfilment of “no evidence of disease activity” (NEDA-3). We evaluated BL-sNfL, 12M-sNfL and BL/12M sNfL ratio (sNfL-ratio) as predictors for treatment response. We followed 14 patients for a median of 41.5 months (range 24.0–50.0). NEDA-3 was fulfilled by 71%, 57% and 36% for a period of 12, 24 and 36 months, respectively. We observed clinical relapses in four (29%), MRI activity in six (43%) and EDSS progression in five (36%) patients. CLAD significantly reduced sNfL (BL-sNfL: mean 24.7 pg/mL (SD ± 23.8); 12Mo-sNfL: mean 8.8 pg/mL (SD ± 6.2); p = 0.0008). We found no correlation between BL-sNfL, 12Mo-sNfL and ratio-sNfL and the time until loss of NEDA-3, the occurrence of relapses, MRI activity, EDSS progression, treatment switch or sustained NEDA-3. We corroborate that CLAD decreases neuroaxonal damage in MS patients as determined by sNfL. However, sNfL at baseline and at 12 months failed to predict clinical and radiological treatment response in our real-world cohort. Long-term sNfL assessments in larger studies are essential to explore the predictive utility of sNfL in patients treated with immune reconstitution therapies.

Real‐World Study of Serum Neurofilament Light Chain Levels in Ocrelizumab‐Treated People with Relapsing Multiple Sclerosis

“…ARR, disability progression (by EDSS, T25FW, and 9HPT), and MRI activity at 12 months were not associated with sNfL levels at baseline. The MRI finding of Gd+ lesions at OCR onset was moderately correlated with baseline sNfL levels (0.458. p=0.012), in line with the study by Cross et al [23] NEDA-3 was reached in 70% of the PwMS, very similar to other results obtained using highefficacy DMTs [31,44]. After 12 months of OCR treatment, the ARR was reduced in 83%, the EDSS was maintained, and there was an 80% reduction in those with radiological activity.…”

“…The significant reduction in sNfL levels verifies the molecular effect of OCR on neurodegeneration in PwMS and was observed at three months after the first infusion, earlier than reported for other DMTs [27]. The 16% decrease in sNfL levels at 12 months was lesser than described in the OBOE study with OCR [23] or in the study with CLD [31].…”

“…Various studies of PwMS have described a reduction in sNfL levels with the start of DMTs, which have demonstrated moderate (teriflunomide (TFL) [26], dimethyl fumarate (DMF) [27] or high natalizumab (NTZ) [28], fingolimod (FGL) [29]], alemtuzumab (ALM) [30], cladribine (CLD) [31] OCR [22], ofatumumab (OFT) [32] effectiveness.…”

Magnetic Resonance Imaging Evidence Supporting the Efficacy of Cladribine Tablets in the Treatment of Relapsing-Remitting Multiple Sclerosis

“…Cladribine tablets were also able to regulate the serum neurofilament (sNfL) levels, a marker with a key role in both monitoring treatment response and capturing long-term disease outcomes [ 69 , 70 ]. Data from the MAGNIFY-MS study and real-world cohorts showed a significant reduction of sNfL as early as 6 months after the initiation of treatment with cladribine tablets that was maintained for up to 2 years [ 13 , 71 , 72 ]. Beyond that, further analyses of MAGNIFY-MS data have investigated the association between changes in sNfL levels and MRI outcomes in patients stratified as (1) no, (2) residual, or (3) resolved CUA lesions.…”

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France

“…Annual immunophenotyping to monitor memory B cells may therefore provide another predictive marker of future MS disease activity [ 85 , 86 ]. CladT has been shown to reduce serum neurofilament light chain (sNfL), a biomarker of axonal damage in MS, although further validation of this biomarker is needed to predict who may need re-treatment with CladT [ 87 ].…”