4 days ago
Tezepelumab Curbs Oral Corticosteroid Use in Severe Asthma
The addition of tezepelumab to standard treatment allowed half the adults with severe asthma to discontinue their use of oral corticosteroids (OCS) after 1 year, according to new data from nearly 300 individuals.
Tezepelumab, a human monoclonal antibody, has been associated with reduction in the use of OCS in patients with OCS-dependent asthma, David J. Jackson, MD, professor and clinical director, Guy's Severe Asthma Centre at Guy's Hospital King's College London, London, England, and colleagues wrote in an abstract presented at American Thoracic Society (ATS) 2025 International Conference.
Many patients with severe asthma take OCS, but previous research has shown associations between extended OCS use and increased risk for a range of side effects including osteoporosis and fractures, hypertension, and infections, and more strategies are needed to help these patients reduce OCS use, the researchers noted.
'We know prolonged oral corticosteroid use leads to adverse effects, including bone, cardiovascular, metabolic, gastrointestinal and psychiatric disorders, and adrenal insufficiency,' Jackson said in an interview. 'The WAYFINDER trial is a multicenter, open-label, single-arm trial evaluating the efficacy and safety of tezepelumab compared to placebo in severe asthma patients who require maintenance use of OCS alongside their standard treatment,' he said.
A previous phase 3 OCS-sparing study known as SOURCE did not meet its primary endpoint, but patients with baseline blood eosinophil counts ≥ 150 cels/μL who received tezepelumab achieved a reduction in daily maintenance OCS (mOCS) dose compared with placebo patients, the researchers wrote in their abstract.
'The WAYFINDER trial was designed to accelerate data collection and specifically address the complexities in the SOURCE trial design that may have contributed to the result of the primary endpoint,' Jackson told Medscape Medical News .
The WAYFINDER trial enrolled 298 adults with severe asthma who had received OCS for at least 3 months before starting the study. All participants received 210 mg of subcutaneous tezepelumab every 4 weeks for up to 52 weeks after a 4-week induction period. The co-primary endpoints were the proportion of patients who reduced their daily mOCS to 5 mg/d or less or discontinued OCS without loss of asthma control.
A total of 273 patients completed the study; the mean baseline mOCS was 10.8 mg/d, and patients were assessed at 28 weeks and 52 weeks.
Overall, 88.9% and 89.9% of patients reduced their mOCS to 5 mg/d or less by week 28 and week 52, respectively, while 32.2% and 50.3% discontinued OCS at these time periods, respectively.
In a post hoc analysis, 82.2% of patients whose reason for systemic corticosteroids was related to adrenal insufficiency achieved an mOCS dose of 5 mg/d or less without loss of asthma control at week 52.
The study was limited by the open-label design, but the safety profile was consistent with previous studies of tezepelumab, researchers said. A 2023 meta-analysis of safety data on tezepelumab for uncontrolled asthma showed that the most common adverse events were nasopharyngitis, headache, and bronchitis, and most AEs occurred within a month of starting tezepelumab. Rates of serious adverse events were lower in patients receiving tezepelumab than those receiving placebo in a pooled analysis.
The standout findings from the study are the clinically meaningful reductions in maintenance OCS use or complete discontinuation achieved with tezepelumab among a broad severe asthma patient population, Jackson told Medscape Medical News .
In addition, two thirds of participants remained exacerbation-free despite OCS dose reductions, and the OCS-sparing effect of tezepelumab was observed across pre-specified patient subgroups, including those defined by baseline blood eosinophil counts (BEC), fractional exhaled nitric oxide (FeNO) level and allergy status, Jackson said.
'These findings reinforce tezepelumab's efficacy in severe asthma as the first and only biologic targeting thymic stromal lymphopoietin (TSLP) with demonstrated efficacy for severe asthma patients across phenotypes and irrespective of biomarker levels including BEC, allergic status, and FeNO,' he said.
Improving Short-Term Health and Long-Term Wellness
'For people living with severe asthma, achieving stable control and reducing or eliminating reliance on oral corticosteroids is a critical goal, not only for respiratory health but also for long-term well-being,' Jackson told Medscape Medical News .
'By showing the benefit of targeting TSLP at the top of the inflammatory cascade and controlling asthma effectively with tezepelumab, we may be able to reduce these risks from OCS and significantly improve control for patients living with severe asthma,' Jackson said. 'We look forward to sharing a manuscript in the future for the phase 3b WAYFINDER study,' he added.
Support for Steroid-Sparing
The current study highlights an important population: Patients with asthma who are dependent on OCS, said Sucharita Kher, MD, pulmonologist and vice chair of clinical operations and quality for the Department of Medicine at Tufts Medical Center, in an interview.
The endpoint tapering OCS without loss of asthma control is clinically meaningful because of the known side effects of OCS, said Kher, who was not involved in the study. The results were not unexpected, but more details on whether patients with eosinophils below 150 cells/µL also benefitted from tezepelumab would be helpful, Kher noted.
The data are exciting because they suggest another option for patients with OCS dependent asthma, said Kher. 'The data also guide clinicians to adopt a strategy to wean patients off OCS when on tezepelumab with the goal of reducing OCS exposure and hence, side effects of prolonged OCS use,' she said. 'We know that OCS have side effects and negative consequences on factors including bone health, blood pressure, and blood sugar control and infection risk,' she added.
Potential barriers to expanding the use of tezepelumab for reducing OCS in asthma patients exist at the patient and healthcare systems levels, Kher told Medscape Medical News .
Patient-level barriers include cost sharing, worry/hesitancy about injections, lack of specialty access, and patient health literacy, she said. In addition, healthcare system barriers include a lack of knowledge on the part of primary care providers, and even some specialty physicians, of the benefits of biologics for severe asthma, said Kher. Other potential challenges include limited infrastructure in clinician offices, such as trained personnel and staff to navigate prior auth/insurance mandates, pre-authorization barriers, and denials based on tiers by insurance companies, she noted.
'Overcoming the barriers requires a multipronged approach, improving awareness and education for healthcare professionals, improve access to specialty care for patients, and advocacy to reduce the processes for insurance approvals,' Kher said.
