BTK Inhibition With Rilzabrutinib Improves Symptoms in Uncontrolled Asthma
Bruton’s tyrosine kinase (BTK) inhibition with rilzabrutinib was associated with improved asthma symptom control in patients with moderate-to-severe disease, despite withdrawal of background therapy, according to a phase 2 randomized trial. The findings suggest a potential novel immunologic mechanism for managing uncontrolled asthma.
The double-blind, placebo-controlled study enrolled 196 adults with persistent symptoms despite inhaled corticosteroids and long-acting β2-agonists. Participants were randomized to receive rilzabrutinib at either 800 mg or 1200 mg daily or placebo, with background therapy tapered between weeks 4 and 9 and resumed at week 12.
The primary endpoint, loss of asthma control (LOAC), occurred less frequently with rilzabrutinib than placebo in both dose groups, though differences did not reach statistical significance. LOAC events occurred in 38% of patients receiving 800 mg versus 50% with placebo, and in 19% receiving 1200 mg versus 29% with placebo.
Improvements in symptom control were observed early and sustained. Asthma Control Questionnaire scores improved by week 2 and remained significantly better through week 12 compared with placebo, even without background therapy. The authors reported that “continued meaningful asthma symptom improvements over 12 weeks were observed, despite background therapy withdrawal.”
Safety outcomes were consistent across dose groups. The most common adverse event was diarrhea, and importantly, no increase in infection risk was observed with rilzabrutinib. The study supports a favorable safety profile for BTK inhibition in this population.
Reference
Maspero J, Pavord I, Wechsler M et al. Rilzabrutinib for patients with moderate-to-severe asthma with uncontrolled symptoms: a double-blind, placebo-controlled, phase 2 study. The Lancet Respiratory Medicine, 2026; 14, 405-416.
