Tezepelumab Reduces Maintenance Oral Corticosteroid Use in SUNRISE Trial

Key Takeaways

• Tezepelumab was associated with greater oral corticosteroid reduction than placebo at week 28 while asthma control was maintained.
• Adverse events occurred in 47 (57%) tezepelumab recipients and 28 (72%) placebo recipients, while serious adverse events occurred in seven (8%) and five (13%), respectively.
• The trial ended early because of recruitment challenges, and the authors concluded that tezepelumab led to greater reductions in daily oral corticosteroid dose than placebo at week 28, with no safety concerns identified for tezepelumab.

Adults with severe oral corticosteroid-dependent asthma receiving tezepelumab in the SUNRISE phase 3 trial had greater odds of a higher category of maintenance oral corticosteroid reduction than those receiving placebo at week 28, with an odds ratio of 2.93 (95% CI, 1.43 to 6.03; p=0.0034). The comparison assessed maintenance oral corticosteroid reduction at week 28 while asthma control was maintained. No safety concerns were identified for tezepelumab.

SUNRISE was a phase 3, double-blind, placebo-controlled trial conducted across 63 sites in 12 countries. Eligible participants were adults aged 18–80 years with physician-diagnosed severe oral corticosteroid-dependent asthma. They had undergone oral corticosteroid optimisation and had received medium-dose or high-dose inhaled corticosteroids for at least 12 months before screening. Participants, investigators, and site staff were masked, and randomization was 2:1 to tezepelumab 210 mg subcutaneously or placebo every 4 weeks for 28 weeks. The primary endpoint was the categorised percentage reduction from baseline in daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control.

The primary analysis and safety outcomes were assessed in the full analysis set. Among treated participants, 122 of 207 planned participants received study drug, including 83 assigned to tezepelumab and 39 to placebo. The study was terminated early because of recruitment challenges, with 90 (74%) participants completing treatment and 25 (20%) not completing the study because of early termination. At week 28, daily oral corticosteroid dose reduction was greater with tezepelumab than with placebo.

Safety findings centered on deaths and exacerbations rather than new concerns. Three deaths occurred, including two in the tezepelumab group during the post-treatment period and one in the placebo group during treatment. Investigators did not consider any of those deaths causally related to study treatment. Over 28 weeks, 25 (30%) tezepelumab recipients and 23 (59%) placebo recipients had at least one asthma exacerbation. No safety concerns were identified for tezepelumab.

Despite early termination, the authors concluded that tezepelumab led to greater reductions in daily oral corticosteroid dose than placebo at week 28.