Disproportionate increase in COPD exacerbation risk for three months after discontinuing LAMA.

<bold>Background:</bold> Adherence to inhaled COPD treatments is suboptimal, with frequent cycles of treatment initiation and withdrawal observed in real-world setting. We explore potential treatment withdrawal effects of LAMA on exacerbations. <bold>Methods:</bold> FLAME, a 52-weeks RCT compared LABA+LAMA with LABA+ICS in patients with moderate-to-severe COPD and a history of exacerbations. In a post-hoc analysis, we selected participants that were receiving LAMA at baseline and we compared exacerbation outcomes between those who continued versus those who discontinued LAMA during the trial. Withdrawal effects were defined as an early spike in exacerbation rates after LAMA discontinuation, that later diminished. Multivariable regression models were used to evaluate these effects. <bold>Results:</bold> Our analysis showed that LAMA discontinuation was linked to an early, transient increase in exacerbation rates. Patients who stopped LAMA experienced a clear early rise in moderate-to-severe exacerbations, including those needing systemic corticosteroids and those needing antibiotics, which then subsided over time. We observed a similar trend for severe exacebations. <bold>Conclusion:</bold> These findings suggest that stopping LAMA may trigger withdrawal effects that cause a temporary surge in COPD exacerbations. These findings emphasise the importance of ensuring treatment adherence in COPD and of accounting for withdrawal effects in clinical trials. <fig><object-id>erj;66/suppl_69/PA5702/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>