BTK inhibitors match Aubagio at reducing relapse rates in MS: Review
Further studies needed to determine if they provide lasting benefits
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- BTK inhibitors match Aubagio for relapse reduction in relapsing multiple sclerosis.
- BTK inhibitors show short-term disability benefits; Aubagio better reduces brain lesions.
- Long-term studies are needed to confirm sustained disability benefits of BTK inhibitors.
Experimental Bruton’s tyrosine kinase (BTK) inhibitors, such as tolebrutinib or evobrutinib, are as effective as the approved therapy Aubagio (teriflunomide) at preventing relapses in people with relapsing forms of multiple sclerosis (MS), according to a review of published studies.
The review found the therapies to be equally safe. BTK inhibitors are better at delaying short-term disability progression, while Aubagio is more effective at reducing inflammatory brain lesions.
However, “current evidence does not support prioritizing BTK inhibitors over [Aubagio],” researchers wrote, at least not for short-term control of relapses or for reducing lesions on MRI scans.
Further studies are now needed to determine if BTK inhibitors provide lasting benefits in slowing disability progression.
The study, “Efficacy and safety of Bruton’s tyrosine kinase inhibitors compared to teriflunomide in relapsing multiple sclerosis: A systematic review and meta-analysis,” was published in Multiple Sclerosis and Related Disorders.
BTK inhibitors reduce activity of immune cells involved in relapses
Symptoms of MS result from an immune system attack against the myelin sheath that covers nerve cells. Over time, accumulating damage leads to long-term disability.
Disease-modifying treatments can reduce the frequency of relapses, periods when new symptoms develop or old ones worsen. However, their ability to prevent long-term disability progression, particularly progression occurring independent of relapse activity, remains limited.
BTK inhibitors are a new class of therapies being developed for MS that reduce the activity of immune cells involved in relapses and new MRI activity. They also ease the chronic inflammatory processes inside the brain that contribute to disability progression outside of relapses.
While most clinical trials assessing BTK inhibitors in relapsing forms of MS have compared them against the approved therapy Aubagio, no studies have combined the results to understand how these drugs work as a whole compared with Aubagio.
To address this, a team of researchers in Brazil conducted a meta-analysis of four randomized controlled studies that compared tolebrutinib or evobrutinib with Aubagio in a total of 4,163 patients.
Tolebrutinib approved in UAE, but not in US
Tolebrutinib is approved in the United Arab Emirates for nonrelapsing secondary progressive MS, and also to slow disability accumulation independent of relapse activity in adults with MS. Its approval has been denied in the U.S. Evobrutinib is no longer being developed because it failed to outperform Aubagio in two Phase 3 clinical trials.
Of the 2,076 patients randomly assigned to a BTK inhibitor, 933 received tolebrutinib and 1,143 evobrutinib. The other 2,087 patients were assigned to Aubagio.
The main goal of this analysis was to compare relapse rates between the BTK inhibitor and Aubagio groups. Secondary outcomes included measures of disability worsening at three and six months and changes in lesions.
Results showed that relapse rates were similar between groups. Still, BTK inhibitors reduced the risk of three-month confirmed disability worsening by 19% compared with Aubagio, although there was no significant difference in six-month confirmed disability worsening.
The researchers advised caution when interpreting the results, however, as tolebrutinib significantly delayed both confirmed disability worsening outcomes in its Phase 3 trials, while no differences were observed with evobrutinib.
Long-term studies focusing on sustained disability outcomes are needed to clarify the potential clinical impact of BTK inhibition beyond relapse suppression.
Looking at MRI outcomes, all treatments reduced the formation of new lesions with active inflammation, but Aubagio was significantly better than BTK inhibitors at doing so.
No significant difference was observed in new or enlarging lesions, and side effects and serious side effects were also similar between groups.
Overall, BTK inhibitors and Aubagio appear equally effective and safe for reducing relapses in relapsing forms of MS. BTK inhibitors may offer modest benefits in short-term disability, but longer studies would be needed to determine if they sustain benefits over the years.
“Long-term studies focusing on sustained disability outcomes are needed to clarify the potential clinical impact of BTK inhibition beyond relapse suppression,” the researchers concluded.
