#VisualAbstract: Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis

1. The Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib when compared to placebo treatment in multiple sclerosis patients showed the ability to reduce the number of gadolinium enhancing lesions on MRI imaging.

2. Key clinical outcomes of annualized relapse rates or change in a disability score were not different between patients treated with placebo compared to evobrutinib at 24 weeks. 

Evidence Rating Level: 1 (Excellent)  

Study Rundown: Multiple sclerosis (MS) is a progressive, demyelinating autoimmune disease that forms identifiable lesions in the central nervous system. Clinical goals of treatment are to reduce the frequency of relapse events and to slow disease progression. In addition to clinical measures of treatment efficacy, imaging findings of lesions in the central nervous system can be used as a proxy market for treatment efficacy. B cells involved in autoimmune disease are thought to play a role in MS, and thus augmenting their activity through the BTK signaling cascade may reduce their effect on MS disease progression. This phase 2 trial evaluated the BTK inhibitor evobrutinib compared to placebo and showed high doses of evobrutinib can significantly reduce the number of central nervous system lesions identified on MRI in MS patients, though clinical markers of disease progression were not altered with evobrutinib treatment at 24 weeks.

The strengths of this study include its evaluation of a novel therapy in a progressive disease, study of multiple dosing regimens, and use of dimethyl fumarate (DMF) as a reference therapy. The study is limited by the generalizability of the patient population, limited study size segmented into multiple treatment groups, and lack of comparison between the evobrutinib and DMF groups. Longer trials will be need to determine evobrutinib’s long term efficacy.

Click to read the study in the NEJM (New England Journal of Medicine)