Background

Dimethyl fumarate (DMF) treatment is associated with a decrease in serum neurofilament light chain (sNfL) in patients with relapsing-remitting multiple sclerosis (RRMS). sNfL is an exploratory biomarker of MS disease activity. Additional data describing the association between sNfL and disease activity are needed to further investigate this biomarker as a potential predictor of treatment response, which could enable a more holistic disease monitoring approach to treatment.

Objectives

To describe variation in sNfL levels with respect to clinical and radiological disease activity in DMF-treated patients.

Methods

DMF-treated patients with RRMS and complete 2Y follow-up data were analyzed. Serum samples were collected, and routine clinical and radiological assessments were conducted at baseline (BL) and at regular intervals. sNfL concentrations were measured by Single Molecule Array (SiMoA). Normative sNfL data from a cohort of 135 healthy adult controls (age range 21-82 years) were used as a comparator. Age-normative sNfL cutoffs were defined based on the 95^th percentile of sNfL levels.

Results

Forty-one patients with 2Y follow-up data were included. Mean (SD) age and disease duration were 37.5 (10.1) and 6.0 (6.5) years, respectively, with mean (SD) time on DMF treatment 43.8 (9.15) months. Twenty-nine (70.7%) patients were treated with a previous MS therapy. Nineteen (46.3%) and 22 (53.7%) patients were below and above age-normative sNfL level at BL, respectively. Over 2Y, mean (95% CI) sNfL level decreased from 8.5 (7.1, 10.2) to 3.4 (2.0, 4.0) pg/ml, representing a 36.6% annual decrease, and 60% decrease over 2Y. Patients experienced a 71.1% (95% CI: 38.8%, 86.3%) reduction in ARR from 1Y prior to BL (0.463, 95% CI [0.279, 0.724]) to 2Y (0.134 [0.067, 0.24]), and 75.6% (59.4%, 87.1%) patients were free of new T2 lesions at 2Y. sNfL was below age-normative level in 53.7% (37.6%, 69%) of patients at BL vs 97.6% (85.6%, 99.9%) at 2Y. Patients with sNfL below age-normative level at BL generally remained below this threshold. At 2Y, patients both above and below age-normative sNfL level at BL experienced low cumulative ARR (95% CI) of 0.132 (0.043, 0.307) and 0.136 (0.05, 0.297), respectively, representing reductions of 75% and 66.7%.

Conclusions

DMF-treated patients reached NfL levels approaching that of healthy controls over 2Y with a reduction in disease activity, regardless of sNfL level at BL in this real-world setting. These data support a correlation between reductions in sNfL levels and decreased disease activity over 2Y of treatment, and potential of sNfL as a biomarker of treatment response that could be assessed during treatment in addition to standard of care monitoring.

Supported by: Biogen.

Background

The TREAT-MS study (Paul-Ehrlich-Institut registry: 281) is assessing real-world effectiveness of alemtuzumab in relapsing-remitting multiple sclerosis (RRMS) patients in Germany.

Objectives

Subgroup analysis of TREAT-MS to investigate the effect of the number of prior disease-modifying therapies (DMTs) on the efficacy and safety of alemtuzumab 1 year after the 2nd treatment cycle with alemtuzumab.

Methods

TREAT-MS is a 5-year, observational, longitudinal, noninterventional, open-label, multicenter study of alemtuzumab-treated patients.

Results

As of February 2020, 883 patients were enrolled and 571 patients were observed for 2 years after treatment initiation. Of these, 565 (98.9%) patients entered the first treatment period, 538 (94.2%) patients entered two treatment periods. 13.3% of patients were treatment-naive at baseline, 83.7% had received prior DMTs, and in 3.0% pretreatment was unknown. The interim analysis focussed on the data of patients 1 year after the 2nd treatment phase and was differentiated by the number of previously received DMTs. Patients with 0, 1, 2, and ≥3 pretreatments had a mean number of 1.6, 1.7, 1.4, and 1.8 relapses, respectively, during the last 12 months before alemtuzumab treatment. After alemtuzumab treatment initiation, annualized relapse rate (ARR) in patients with 0, 1, 2, ≥3 pretreatments reached levels of 0.13, 0.18, 0.25, and 0.24. ARR after alemtuzumab initiation was significantly higher in patients who received 2 or ≥3 prior DMTs when compared with treatment-naive patients.

The majority of patients were relapse-free 1 year after the 2nd course of alemtuzumab. 82.2%, 77.0%, 66.5%, 73.1% of the patients with 0, 1, 2, ≥3 pretreatments, respectively, had no relapses during the observational period. The proportion of relapse-free patients 1 year after the second alemtuzumab course was highest in treatment-naive patients.

Mean expanded disability status scale (EDSS) score at baseline was 2.2, 2.4, 2.6, and 3.6 for those who received 0, 1, 2, and ≥3 prior DMTs, respectively, and changed by a mean EDSS value of –0.5, –0.2, –0.2, and –0.5 one year after the 2nd treatment phase.

Adverse events were reported for 64.5%, 66.9%, 66.9%, 73.6% of the patients treated with 0, 1, 2, and ≥3 DMTs. No new safety signals were observed.

Conclusions

The interim subgroup analysis of patients 1 year after the 2nd treatment cycle with alemtuzumab has shown that relapse rates were reduced, and EDSS scores were stable regardless of the number of prior DMTs received. These data confirm registration trial findings (CARE-MS I and II) in the real-world setting in patients with longer disease duration and varying treatment history.