It is time to rethink clinical trials on Bruton's tyrosine kinase inhibitors in multiple sclerosis

The EVOLUTION trials comparing evobrutinib and teriflunomide in multiple sclerosis revealed unexpected negative results, challenging the choice of the annualized relapse rate (ARR) as the primary outcome. While monoclonal antibodies effectively control inflammation, the focus on ARR may not capture the long-term disability progression addressed by Bruton's tyrosine kinase inhibitors (BTKi). This letter questions the suitability of teriflunomide as a comparator due to low relapse rates in the control group, possibly stemming from patient selection bias. The author advocates for a reevaluation of study design, outcomes, and comparators in multiple sclerosis research, emphasizing the need for new approaches to address disease activity and disability progression. It is time to rethink clinical trials on Bruton's tyrosine kinase inhibitors in multiple sclerosis.