Adult patients with severe oral corticosteroid-dependent asthma who received tezepelumab had 2.93 times the odds of achieving a greater reduction in maintenance oral corticosteroid dose compared with those who received placebo while maintaining asthma control, according to a new study.
In the phase 3 SUNRISE trial, researchers randomly assigned 122 adults aged 18 to 80 years with physician-diagnosed asthma taking maintenance oral corticosteroid therapy to receive either tezepelumab 210 mg (n = 83) or placebo (n = 39) administered subcutaneously every 4 weeks for 28 weeks. Eligible participants were receiving medium- or high-dose inhaled corticosteroids and long-acting beta-2 agonists and had a blood eosinophil count of at least 150 cells/μL at screening or documentation of at least 300 cells/μL within the previous 12 months.
The trial was terminated early because of recruitment challenges. At termination, 122 of the planned 207 participants had been enrolled, and 90 of them completed treatment.
The primary endpoint assessed how much patients were able to reduce their daily maintenance oral corticosteroid dose by week 28 without losing asthma control. The odds of reaching a greater category of oral corticosteroid reduction were higher with tezepelumab compared with with placebo.
At week 28, 36% of patients receiving tezepelumab and 21% receiving placebo achieved a 90% to 100% reduction in their oral corticosteroid dose without loss of asthma control. A reduction of at least 50% without loss of asthma control occurred in 69% vs 44% of the participants, respectively, complete discontinuation occurred in 35% vs 21%, respectively, and an oral corticosteroid dose of 5 mg or less was reached in 59% vs 38%, respectively.
Among the patients with baseline blood eosinophil counts of at least 150 cells/μL, the odds of achieving a category of greater percentage reduction in oral corticosteroid dose were 3.48 times higher in the tezepelumab group compared with in the placebo group. Among those with counts of at least 300 cells/μL, the odds were 3.30 times higher. Among patients with counts below 150 cells/μL, the odds ratio was 1.76. The researchers noted that results in the subgroup with counts below 150 cells/μL should be interpreted with caution because of the small number of participants.
At week 28, prebronchodilator forced expiratory volume in 1 second increased by 0.24 L in the tezepelumab group and decreased by 0.03 L in the placebo group. Asthma Control Questionnaire-6 scores changed by −1.23 points with tezepelumab and −0.64 points with placebo. Asthma Quality of Life Questionnaire scores changed by 1.30 points and 0.50 points, respectively.
During the 28-week treatment period, 30% of the patients receiving tezepelumab and 59% of those receiving placebo experienced at least one asthma exacerbation. The annualized asthma exacerbation rate was 0.64 with tezepelumab and 2.04 with placebo. The rates of exacerbations requiring an emergency department visit or hospital admission were 0.09 and 0.67, respectively.
The researchers stated that adverse events occurred in 57% of the patients receiving tezepelumab and 72% of those receiving placebo. Serious adverse events occurred in 8% and 13%, respectively. Three mortalities occurred during the study—two in the tezepelumab group during the posttreatment period and one in the placebo group during treatment—but none of them were considered causally related to study treatment based on investigator assessment.
The researchers identified early study termination and the resulting smaller-than-planned sample size as the main study limitation. They also noted baseline imbalances in blood eosinophil counts and oral corticosteroid doses between the treatment groups and stated that the study was not powered to assess statistical significance within subgroups.
“[T]he results of the SUNRISE trial show the potential of tezepelumab to reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising the efficacy outcomes,” wrote lead study author Michael E Wechsler, MD, of National Jewish Health and colleagues.
The study was funded by AstraZeneca and Amgen. Full disclosures of the study authors can be found in the published study.
Source: The Lancet Respiratory Medicine
