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Randomized Controlled Trial
. 2024 Aug 22;64(2):2400404.
doi: 10.1183/13993003.00404-2024. Print 2024 Aug.

Titration of anti-IL-5 biologics in severe asthma: an open-label randomised controlled trial (the OPTIMAL study)

Marianne Baastrup Soendergaard  1 , Anne-Sofie Bjerrum  2 , Linda Makowska Rasmussen  3 , Sofie Lock-Johansson  4 , Ole Hilberg  5 , Susanne Hansen  6   7 , Anna von Bulow  6 , Celeste Porsbjerg  6
Affiliations
Randomized Controlled Trial

Titration of anti-IL-5 biologics in severe asthma: an open-label randomised controlled trial (the OPTIMAL study)

Marianne Baastrup Soendergaard et al. Eur Respir J. .

Abstract

Background: Anti-interleukin (IL)-5 biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL-5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL-5 biologic.

Methods: In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL-5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible.

Results: Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17%; p=0.13). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout.

Conclusion: This study serves as a proof of concept for titration of anti-IL-5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.

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Conflict of interest statement

Conflict of interest: M.B. Soendergaard reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca, and participation on a data safety monitoring board or advisory board with AstraZeneca. A-S. Bjerrum reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca. L.M. Rasmussen reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK, Teva and ALK, support for attending meetings from AstraZeneca and Chiesi, and participation on a data safety monitoring board or advisory board with AstraZeneca, GSK, Teva and Sanofi. A. von Bulow reports consultancy fees from Novartis, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Novartis and GSK, and participation on a data safety monitoring board or advisory board with AstraZeneca and Novartis. C. Porsbjerg reports grants paid to their institution from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, consultancy fees (paid both to institution and as personal honoraria) from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, payment or honoraria for lectures, presentations, manuscript writing or educational events (paid both to institution and as personal honoraria) from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, and participation on a data safety monitoring board or advisory board (fees paid both to institution and as personal honoraria) with AstraZeneca, Novartis, Teva, Sanofi and ALK. The remaining authors have no potential conflicts of interest to disclose.

Figures

None
Overview of the OPTIMAL study. IL: interleukin.
FIGURE 1
FIGURE 1
The OPTIMAL titration algorithm with assessment of titration ability over 52 weeks. FEV1: forced expiratory volume in 1 s; OCS: oral corticosteroids.
FIGURE 2
FIGURE 2
Flowchart of patients in the OPTIMAL study. IL: interleukin.
FIGURE 3
FIGURE 3
Kaplan–Meier plot of time to first exacerbation in the active and control arms. Boxes indicate timing of dosing interval increase of interleukin (IL)-5 treatment for patients in the active arm.
FIGURE 4
FIGURE 4
a) Forced expiratory volume in 1 s (FEV1), b) Asthma Control Questionnaire (ACQ) and c) blood eosinophils in the active and control arms during the OPTIMAL study.
See this image and copyright information in PMC

Comment in

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