Related Experiment Video
Updated: Jan 8, 2026
Author Spotlight: Evaluating the Therapeutic Efficacy of Moving Cupping Along Meridians for Acute Exacerbation of COPD
Published on: September 27, 2024
Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the
Alexander G Mathioudakis1,2, Sebastian Bate3,4, Victoria Chatzimavridou-Grigoriadou5
1Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK alexander.mathioudakis@manchester.ac.uk.
Background:
In real-world chronic obstructive pulmonary disease (COPD) care, poor adherence often leads to treatment discontinuations. Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited.
Methods:
We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history. Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidence plots during the first quarter of follow-up. Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects.
Results:
Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use). This observation was not confirmed for severe exacerbations, likely due to low event count. In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance. Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count.
Conclusion:
Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials.
Trial Registration Number:
NCT01782326.
More Related Videos
07:10Home-Based Prescribed Pulmonary Exercise in Patients with Stable Chronic Obstructive Pulmonary Disease
Published on: August 24, 2019
04:59Heat-sensitive Moxibustion as a Traditional Chinese Medicine Therapy for Chronic Obstructive Pulmonary Disease Combined with Insomnia
Published on: May 30, 2025
Related Concept Videos
01:26COPD: Management Using Bronchodilators and Corticosteroids
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:24Asthma-III: Symptoms and Complications
Classification of Asthma
01:22Chronic Obstructive Pulmonary Disease
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...
01:25Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
01:30Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes: