Changes in serum total IgE after cessation of tezepelumab after 2 years of treatment (DESTINATION)

Background: In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab gradually decreased serum total immunoglobulin (Ig)E levels in patients with severe, uncontrolled asthma over 52 weeks. In the phase 3 DESTINATION study (NCT03706079), this reduction continued to end of treatment (EOT; week 104). Objective: To assess serum total IgE during the off-treatment extended follow-up (EFU) in DESTINATION, following tezepelumab cessation. Methods: Patients (12–80 years) who completed NAVIGATOR could enrol in DESTINATION, a multicentre, randomized, placebo-controlled, double-blind, extension study. Patients previously randomized to tezepelumab continued treatment (tezepelumab only; 210 mg every 4 weeks). Those previously randomized to placebo were re-randomized 1:1 to placebo (placebo only) or tezepelumab. At EOT, eligible patients could enter a 36-week off-treatment EFU. Change in serum total IgE over time was assessed. Results: Overall, 569 patients entered the EFU. Mean baseline serum total IgE was 586.18 and 625.19 IU/mL for the tezepelumab only and placebo only subgroups. After tezepelumab cessation, serum total IgE remained low; there was a partial increase from week 122, but levels remained below baseline (Figure). Conclusion: Serum total IgE levels reductions achieved with tezepelumab during NAVIGATOR and DESTINATION were maintained for 36 weeks after tezepelumab cessation, suggesting a maintained immunological effect.