Patients discontinuing long-acting muscarinic antagonists (LAMA) or inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD) experienced a significant increase in exacerbation risk for up to three months, according to a post-hoc analysis of the landmark FLAME trial.
The research, published in Thorax, examined data from 3,362 individuals with moderate-to-severe COPD and a history of exacerbations. The original FLAME trial compared the effectiveness of a long-acting beta-2 agonist (LABA) combined with a LAMA to a LABA plus ICS regimen in reducing COPD exacerbations. This new analysis focused on identifying potential “withdrawal effects” following the cessation of either LAMA or ICS treatment.
Investigators observed a marked, transient increase in moderate-to-severe exacerbations during the first quarter of follow-up among patients who stopped using a LAMA, particularly those not concurrently using an ICS. The rate of exacerbations in this subgroup rose by up to 2.2 times compared to those who continued LAMA therapy (95% confidence interval 1.2 to 4.1). While the increase was statistically significant (p=0.001), the researchers noted that a similar trend wasn’t observed for severe exacerbations, likely due to the relatively small number of such events.
Discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), although the difference in moderate-to-severe exacerbations did not reach statistical significance. Importantly, the ICS withdrawal effect appeared consistent regardless of a patient’s baseline blood eosinophil count, a biomarker often used to guide COPD treatment decisions.
The FLAME trial, conducted between 2013 and 2016, investigated whether a once-daily LABA/LAMA treatment—indacaterol-glycopyrronium—would be as effective as twice-daily LABA/ICS therapy—salmeterol-fluticasone—in reducing exacerbations. The study, detailed in the New England Journal of Medicine in 2016, initially showed comparable efficacy between the two treatment approaches.
The recent post-hoc analysis underscores the importance of adherence to prescribed COPD medications and careful consideration when making changes to treatment regimens. The findings suggest clinicians should be aware that the initial three months following the discontinuation of either a LAMA or ICS may represent a period of heightened risk for exacerbations.
