STOPPING LAMA or ICS in COPD, raised exacerbation risk for three months, with pronounced withdrawal-associated spikes.
COPD Exacerbation Risk After Treatment Discontinuation
Poor adherence in chronic obstructive pulmonary disease (COPD) often results in treatment discontinuations, yet the short-term consequences of stopping inhaled therapies are not always anticipated. In a post hoc analysis of the 52-week, double-blind FLAME trial, investigators examined whether early shifts in exacerbation patterns signaled withdrawal effects after discontinuing long-acting muscarinic antagonists (LAMA) or inhaled corticosteroids (ICS).
The parent trial compared a long-acting beta-2 agonist (LABA) plus LAMA regimen with LABA plus ICS in 3,362 patients with moderate-to-severe COPD and a history of exacerbations. Monthly exacerbation incidence plots suggested that the first quarter of follow-up carried a different risk pattern than later quarters, prompting an analysis focused on timing.
COPD Exacerbation Risk After LAMA or ICS Discontinuation
Participants were stratified by baseline use of LAMA or ICS, then outcomes were compared between the first quarter and subsequent quarters among those who continued versus discontinued each treatment. Multivariable mixed-effects models were used to evaluate differences in exacerbation rates, with temporal variation interpreted as consistent with withdrawal effects.
Discontinuing LAMA was associated with a marked, transient rise in moderate-to-severe exacerbations during the first quarter compared with later quarters (p=0.001). In the subgroup judged least influenced by concomitant ICS use, the rate ratio increased up to 2.2 (95% CI 1.2–4.1) in the early period. This signal was not confirmed for severe exacerbations, which the authors attributed to low event counts.
In contrast, discontinuing ICS was linked to a significant early increase in severe exacerbations (p=0.023), while the difference for moderate-to-severe events did not reach statistical significance. Notably, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count.
Clinical Takeaway
These findings suggest that both LAMA and ICS discontinuation may produce meaningful, time-limited withdrawal effects on exacerbations. For clinicians, the results reinforce the importance of supporting adherence and planning therapy changes with awareness that the first few months after discontinuation may represent a higher-risk window.
Reference: Mathioudakis AG et al. Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial. Thorax. 2025;doi:10.1136/thorax-2025-223282.
