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

Eur Respir J. 2024 Aug 22;64(2):2400404. doi: 10.1183/13993003.00404-2024. Print 2024 Aug.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Algorithms*
  • Anti-Asthmatic Agents* / administration & dosage
  • Anti-Asthmatic Agents* / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Asthma* / drug therapy
  • Biological Products / administration & dosage
  • Biological Products / therapeutic use
  • Female
  • Humans
  • Interleukin-5* / antagonists & inhibitors
  • Male
  • Middle Aged
  • Pilot Projects
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Interleukin-5
  • Anti-Asthmatic Agents
  • Biological Products
  • Antibodies, Monoclonal, Humanized
  • IL5 protein, human