Baseline neurofilament light chain (NfL) levels may be a biomarker of future lesion activity observed during magnetic resonance imaging (MRI) and relapse risk among patients with multiple sclerosis (MS), according to study results presented at the 2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) held from June 1-4, in National Harbor, Maryland.

Evobrutinib, a highly selective Bruton tyrosine kinase inhibitor, was found, in a post hoc analysis of phase 2 clinical trial data (ClinicalTrials.gov identifier: NCT02975349), to significantly lower NfL levels at weeks 12 and 24. As NfL is a biomarker of neuroaxonal damage in MS, this study aimed to evaluate the prognostic value of baseline NfL for predicting clinical relapse and change in MRI lesion activity.

Patients (N=162) with MS who received 75 mg evobrutinib once or twice daily, 25 mg evobrutinib once daily, or placebo were evaluated for the association between baseline NfL levels with qualified relapse over 24 weeks and MRI lesion activity at weeks 12, 16, 20, and 24. Low NfL was defined as <11.36 pg/mL.


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Patients who had high baseline NfL also had high disease burden at baseline coupled with increased rates of clinical relapse and MRI lesion activity over the 24-week study period.

Compared with a pooled cohort of patients who received placebo or 25 mg evobrutinib, patients who received high dose evobrutinib were associated with reduced qualified relapse risk after stratifying by baseline NfL (odds ratio [OR], 0.12; P =.0028).

No significant interaction was observed between baseline NfL levels and the cumulative number of MRI lesions, in which high dose evobrutinib associated with decreases in Gd+T1 lesions (relative reduction [RR], 69.4%; P =.0102) and new or enlarging T2 lesions (RR, 73.4%; P =.0012) compared with placebo among patients with low baseline NfL. Similarly, high NfL associated with 69.2% (P =.0018) and 54% (P =.0458) RRs in Gd+T1 and new or enlarging T2 lesions, respectively.

This study was limited by the small sample size and the post hoc design. Additional confirmation study is needed.

“The data indicate that higher doses of evobrutinib reduce MRI activity, regardless of baseline NfL levels, and significantly reduce the proportion of patients with relapses vs placebo/low doses in the high blood NfL level group,” the researchers concluded. “These data also support the value of blood NfL levels as a prognostic marker of future disease activity.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Kuhle J, Kappos L, Montalban X, et al. Evobrutinib Significantly Reduces Relapses and Magnetic Resonance Imaging Outcomes in Patients With Multiple Sclerosis: Association With Baseline Neurofilament Light Chain Levels. Presented at: CMSC 2022 Annual Meeting; June 1-4, 2022; National Harbor, Maryland. Abstract DMT18.