The following article is part of conference coverage from the 2022 American Academy of Neurology (AAN) Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the 2022 AAN Annual Meeting.

 

Evobrutinib, a highly selective Bruton’s tyrosine kinase inhibitor (BTKi), decreased slowly expanding lesion (SEL) volume in patients with relapsing multiple sclerosis (MS) in a dose-dependent manner, according to study findings presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, held from April 2 to April 7 in Seattle, Washington, and virtually from April 24-26, 2022.


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SELs are defined as chronically active, demyelinated lesions that are likely to be driven by sustained microglia/macrophage activity. SELs are associated with irreversible neural tissue damage and axonal loss. Evobrutinib is known to target B cells, macrophages, and microglia, with a 2021 phase 2 trial (ClinicalTrials.gov Identifier: NCT02975349) showing that treatment with evobrutinib 75 mg twice daily reduced T1 gadolinium-enhancing lesions as week 24 vs placebo. The objective of the current study was to assess the effect of evobrutinib vs a comparator treatment on SEL volume from baseline to week 48 in patients with relapsing MS.

SELs were detected with the use of magnetic resonance imaging (MRI) as radially expanding areas of preexisting transverse relaxation time (T2) lesions of 10 or less contiguous voxels with a size of approximately 30 mm. In the current study, the analysis of SEL volume, which was stratified by baseline T2 lesion volume tertiles, was based on week 48 end-of-treatment values among completers plus discontinuers.

The following evobrutinib dose groups — evobrutinib 25 mg once daily (n=50), evobrutinib 75 mg once daily (n=51), and evobrutinib 75 mg twice daily (n=53) — were compared with placebo plus evobrutinib 25 mg once daily (n=53). Pooled groups (ie, high-dose evobrutinib 75 mg once daily and evobrutinib 75 mg twice daily vs low-dose placebo plus evobrutinib 25 mg once daily) were used for subgroup analyses.

Study findings revealed that relative to the comparator, SEL volume decreased with increasing evobrutinib doses (evobrutinib 25 mg once daily, –136.5 mm3 [P =.505]; evobrutinib 75 mg once daily, –246.0 mm3 [P =.192]; and evobrutinib 75 mg twice daily,
–474.5 mm3 [P =.047]).

SEL volume was significantly reduced with high-dose evobrutinib vs low-dose evobrutinib within the following subgroups: baseline Expanded Disability Status Scale (EDSS) 3.5 or less (–652.0 mm3 [P =.020]); relapsing-remitting MS (–317.0 mm3 [P =.025]); and longer duration of disease (8.5 years or less; –729.3 mm3 [P =.040]). Analysis of the SEL volume as a percentage of the baseline T2 lesion volume yielded similar findings.

The researchers concluded that the use of evobrutinib in patients with relapsing MS decreases SEL volume in a dose-dependent fashion, which is particularly evident among those with more advanced disease. “This is the first evidence that a BTKi impacts brain lesions associated with chronic inflammation and tissue loss, probably via microglia,” they concluded.

This is the first study to demonstrate that the use of a BTKi affects the brain lesions associated with chronic inflammation and tissue loss in patients with relapsing MS, likely via microglia.

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  

Reference

Arnold D, Elliott C, Montalban X, Martin E, Hyvert Y, Tomic D. Effects of evobrutinib, Bruton’s tyrosine kinase inhibitor, on slowly expanding lesions: an emerging imaging marker of chronic tissue loss in multiple sclerosis. Presented at: the 2022 AAN Annual Meeting; April 2-7, 2022; Seattle, Washington; April 24-26, 2022; Virtual Meeting. Abstract S14.009.