Multiple sclerosis: oral BTK inhibitor quells MRI disease activity

Takeaway

• An orally administered Bruton’s tyrosine kinase (BTK) inhibitor reduces gadolinium-enhancing lesions in patients with relapsing multiple sclerosis.

Why this matters

• Patients experience ongoing relapses, disability progression despite available treatments.

Key results

• Mean total number of gadolinium-enhancing lesions during weeks 12-24:
  • 3.85 placebo,
  • 4.06 evobrutinib 25 mg once daily,
  • 1.69 evobrutinib 75 mg once daily,
  • 1.15 evobrutinib 75 mg twice daily, and
  • 4.78 dimethyl fumarate.
• Baseline-adjusted rate ratio for total number of lesions over time vs placebo:
  • 1.45 evobrutinib 25 mg once daily (P=.32),
  • 0.30 evobrutinib 75 mg once daily (P=.005), and
  • 0.44 evobrutinib 75 mg twice daily (P=.06).
• Unadjusted annualized relapse rate at week 24:
  • 0.37 placebo,
  • 0.57 evobrutinib 25 mg once daily,
  • 0.13 evobrutinib 75 mg once daily,
  • 0.08 evobrutinib 75 mg twice daily, and
  • 0.20 dimethyl fumarate.
• No significant differences in change in Expanded Disability Status Scale score.
• Evobrutinib associated with elevated liver aminotransferase levels.

Study design

• Phase 2 randomized controlled trial among 267 adult patients with relapsing multiple sclerosis.
• Randomization: double-blind placebo vs evobrutinib (multiple doses) vs open-label dimethyl fumarate.
• Main outcome: total (cumulative) number of gadolinium-enhancing lesions on T₁-weighted MRI.
• Funding: EMD Serono.

Limitations

• Small trial, limited duration.
• Patients older, longer disease duration, fewer recent relapses vs other trials.