Phase 3 data suggest tezepelumab can help patients with severe oral corticosteroid-dependent asthma cut steroid use without sacrificing control.
Patients with severe asthma dependent on long-term oral corticosteroids may finally have a viable pathway to reducing steroid exposure, researchers say.
The phase 3 SUNRISE trial has showed tezepelumab significantly lowered maintenance steroid requirements while maintaining asthma control.
According to the results published in The Lancet Respiratory Medicine, the multicentre, placebo-controlled trial found patients treated with tezepelumab had nearly three times greater odds of achieving larger reductions in oral corticosteroid dose compared with placebo over 28 weeks.
The researchers described the findings as particularly important given the well-established burden associated with long-term oral corticosteroid use, including cardiovascular, metabolic, psychiatric, skeletal and ophthalmological complications, many of which can be irreversible.
“The results of SUNRISE suggest that patients receiving tezepelumab can reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising the efficacy outcomes,” they wrote.
“These findings suggest that, in clinical practice, tezepelumab could provide a potential oral corticosteroid-sparing treatment option for patients with severe, oral corticosteroid-dependent asthma.”
The study enrolled adults aged 18 to 80 years with severe asthma who had required maintenance oral corticosteroids for at least six months despite treatment with medium- or high-dose inhaled corticosteroids and long-acting beta agonists.
Participants also needed a history of at least one exacerbation in the previous two years and evidence of eosinophilic inflammation.
After optimisation of steroid dosing, patients were randomised 2:1 to receive subcutaneous tezepelumab 210mg or placebo every four weeks for 28 weeks. Oral corticosteroids were progressively tapered during the study while monitoring for loss of asthma control.
The primary endpoint was met despite the study being terminated early because of recruitment difficulties linked to changing clinical practice and greater access to biologics. Of the planned 207 participants, only 122 were ultimately randomised.
Even with the smaller sample size, the researchers said the treatment effect remained statistically significant. The odds ratio for achieving a greater category of oral corticosteroid reduction at week 28 was 2.93 in favour of tezepelumab.
More than a third of patients receiving tezepelumab achieved a 90-100% reduction in oral corticosteroid dose while maintaining asthma control, compared with 21% receiving placebo.
Nearly 70% achieved at least a 50% reduction, and 35% were able to completely discontinue maintenance oral corticosteroids.
The mean daily steroid dose at week 28 fell to 6.3mg in the tezepelumab arm versus 8.3mg with placebo.
The biologic’s benefits extended beyond steroid reduction, the researchers found.
Patients treated with tezepelumab experienced substantially fewer exacerbations, with annualised exacerbation rates reduced by almost 70% compared with placebo.
Only 30% of tezepelumab-treated patients experienced at least one exacerbation during the study period compared with 59% in the placebo arm. Rates of exacerbations requiring emergency department presentation or hospital admission were also markedly lower.
Lung function improvements were clinically meaningful, with pre-bronchodilator FEV1 improving by 0.24L in the tezepelumab group compared with a slight decline in the placebo arm.
Improvements in asthma control questionnaire scores and quality-of-life measures were also observed as early as week four and sustained throughout treatment.
The researchers said the findings reinforced tezepelumab’s role as an upstream biologic targeting thymic stromal lymphopoietin, an epithelial cytokine implicated in multiple inflammatory pathways involved in asthma pathophysiology.
“Participants who received tezepelumab had higher odds of reducing their daily maintenance oral corticosteroid dose than participants who received placebo in the overall population and across baseline BEC subgroups,” they concluded.
“In addition, compared with placebo, tezepelumab treatment led to reductions in exacerbations, and improvements in lung function, asthma symptom control, and HRQoL in patients with severe, oral corticosteroid-dependent asthma.”
The study also offered a clearer signal than the earlier SOURCE trial, which failed to meet its primary steroid-sparing endpoint. SUNRISE investigators argued that stricter steroid tapering protocols and stopping rules likely reduced the placebo effect that complicated interpretation in SOURCE.
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An accompanying editorial said the trial arrived at a time when “steroid stewardship” had become increasingly urgent in severe asthma management.
The authors also pointed to the changing therapeutic landscape that made SUNRISE harder to complete, arguing the recruitment challenges themselves reflected progress in severe asthma care as fewer patients remain on chronic oral corticosteroids.
“Conducting placebo-controlled oral corticosteroid-sparing clinical trials for severe asthma is becoming increasingly challenging, as more biologics become available and fewer patients require long-term oral corticosteroids,” they wrote.
“Some patients with poorly controlled asthma and frequent exacerbations could still have repeated steroid exposures but might not be on long-term daily oral corticosteroids.
“Equally important, SUNRISE again challenges the efficacy of biologics in patients with type-2-low asthma.”
While tezepelumab showed benefit across eosinophil subgroups, the magnitude of steroid reduction and lung function improvement was greater among patients with higher eosinophil counts.
“For patients consigned to long-term oral corticosteroid therapy, biologics offer a viable pathway to long-term oral corticosteroid liberation,” the authors of the editorial concluded.
“The SUNRISE study, despite its limitations, closes a clinically relevant gap in the tezepelumab database of its corticosteroid-sparing effect, reinforcing the role of biologics in preventing long-term oral corticosteroid exposure and potentially leading to disease remission in patients with severe asthma.
“As the therapeutic armamentarium expands, so too does our responsibility to practice rigorous steroid stewardship.”
