Tezepelumab cuts OCS use in OCS-dependent patients with severe asthma

Patients with severe asthma who were dependent on oral corticosteroid (OCS) were able to reduce their use of maintenance OCS after treatment with the monoclonal antibody tezepelumab, according to findings from the interim analysis of the phase IIIb WAYFINDER trial.

“The proportion of patients who reduced their maintenance OCS dose to ≤5 mg/day increased over time,” said Dr Bill Cook from BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, US, during his poster presentation at ACAAI 2023.

The percentage of patients achieving this outcome drastically jumped from week 4 to week 12 (from 38.6 percent to 84.4 percent). This continued to increase up until week 28 to 100 percent, which was sustained until week 32. Mean follow-up period was 17.9 weeks. [ACAAI 2023, abstract P102]

The fraction of patients with ≥50-percent reduction in OCS dose also increased over time. At week 4, only 2.4 percent of participants were able to achieve this endpoint. By week 8, this jumped to 41.7 percent and continued to increase until week 32 (100 percent).

In an OCS-sparing phase III study, ≥90 percent reduction in OCS dose was achieved by a similar fraction of patients who were treated with tezepelumab or placebo (54 percent vs 46 percent). [Lancet Respir Med 2022;10:650-660] “However, a greater reduction in OCS dose was seen with tezepelumab than with placebo in patients with a baseline blood eosinophil count of ≥150 cells/uL,” noted Cook and colleagues.

“[In the current analysis, we sought to evaluate] the ability of tezepelumab in reducing the prescribed OCS dose without losing asthma control,” they continued.

Eighty-four adults who met the inclusion criteria* were administered tezepelumab 210 mg Q4W subcutaneously for up to 52 weeks (mean age 55.6 years, 65.5 percent female). The induction phase ran from week 0 to 4; following which, the OCS reduction and maintenance phase ran until week 52. The predefined OCS dose titration schedule during the reduction phase depended upon the initial OCS dose, or the dose at the time of re-evaluation, and hypothalamic-pituitary-adrenal axis evaluation.

Median daily maintenance OCS dose was 10 mg. Three-quarters of the cohort were receiving ≤10 mg OCS dose daily. Mean Asthma Control Questionnaire-6 (ACQ-6) score was 2.8.

Asthma endpoints, safety

Post-bronchodilator FEV₁ was generally stable from baseline (mean, 1.94 L) to week 28 (mean, 1.96 L).

Mean ACQ-6 score also dropped over time. At week 4, the mean absolute change from baseline in ACQ-6 score was -0.40. By week 28, this was down to -1.27.

The safety findings of WAYFINDER were also consistent with that seen in other phase III trials on tezepelumab. There were only four serious adverse event (SAEs) reported, the most common being asthma (n=3). There were no deaths or treatment discontinuations due to any SAE.

“This early trend analysis of WAYFINDER suggests that patients with severe asthma who were treated with tezepelumab can achieve protocol-driven reductions in the dose of maintenance OCS while maintaining asthma control,” Cook concluded.