COPD Study Analyzes How Initial Treatment Affects Future Exacerbations

In a retrospective analysis of patients with chronic obstructive pulmonary disease (COPD), those whose exacerbations were treated with systemic corticosteroids alone or together with antibiotics, did more poorly than those treated with antibiotics alone, a recent study reported in the International Journal of Chronic Obstructive Pulmonary Disease.

In addition, a first hospitalization predicted subsequent hospitalization, mortality, and premature discontinuation. These findings held true even after adjustment for prior inhaled corticosteroid (ICS) use and exacerbation history.

Exacerbations of COPD are commonly treated with systemic corticosteroids, antibiotics, or both, and sometimes requires hospitalization. It’s unknown if the events have different clinical characteristics or the impact of how the first exacerbation is managed on future exacerbations.

The analysis was done because while exacerbations of COPD are managed differently, it is unknown whether treatment of 1 exacerbation predicts the likelihood of future ones.

The data for this study came from the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial, with the largest number (17,1350) of randomized patients with COPD followed in a long-term randomized trial.

The researchers pooled data from 2 treatment arms, totaling 8061 patients, to see if there were differences in the clinical characteristics, according to the treatment received for their first acute on-treatment exacerbation. They looked to see if the subsequent clinical course differed according to the treatment choices made during the management of the first event.

Participants in TIOSPIR had a diagnosis of COPD with a post-bronchodilator mean forced expiratory volume in 1 second (FEV₁) ≤70% predicted and an FEV₁/FVC ratio ≤0.70. They were aged 40 years or more, with a smoking history of 10 years or more.

All COPD medications were allowed except other inhaled anticholinergic agents and systemic corticosteroid medication at unstable (<6 weeks) or high (chronic; equivalent of 10 mg/day prednisolone) doses. Patients whose first on-treatment exacerbation was moderate or severe were included in the analysis.

Patients received once-daily tiotropium (Spiriva) via Respimat 5 μg (2 inhalations of 2.5 μg), Respimat 2.5 μg (2 inhalations of 1.25 μg), or HandiHaler 18 μg, and the parallel HandiHaler or Respimat placebo. They were reviewed at weeks 0, 6, and 12, and then every 12 weeks. At each visit, data about symptomatic exacerbations, and how these were treated, were collected. An independent mortality adjudication committee attributed the cause of each death.

Exacerbations were defined as the worsening of 2 or more major respiratory symptoms (dyspnea, cough, sputum, chest tightness, or wheezing) for more than 3 days and requiring specified treatment changes.

The severity of exacerbations was defined by the type of treatment received: moderate exacerbations required a prescription for antibiotics, systemic corticosteroids, or both (with no hospitalization) and severe exacerbations required hospitalization (due to COPD). While hospitalized patients commonly received antibiotics and/or corticosteroids, no therapy details were available; these events were analyzed separately (all groups are mutually exclusive).

Of 8061 patients with moderate to severe exacerbation(s), demographics were similar across patients who were hospitalization or treated with antibiotics and/or steroids.

Of the exacerbations treated with systemic corticosteroids, alone or in combination, antibiotics had the highest risk of subsequent exacerbation (hazard ratio [HR], 1.21; P = .0004, and HR, 1.33; P <.0001, respectively), and a greater risk of having a hospitalized, or severe, exacerbation (HR, 1.59 and 1.63, respectively; P <.0001) or death (HR, 1.50; P = .0059 and HR, 1.47; P = .0002, respectively) compared with exacerbations treated with antibiotics alone.

Initial hospitalization led to the highest risk of subsequent hospitalization (HR, 3.35 and 4.31, respectively; P <.0001) or death (all-cause or COPD-related, HR, 3.53 and 5.54, respectively; P <.0001, ) versus antibiotics alone.

The authors said that while they don’t think the results mean that less intensive treatment is beneficial, they think initial therapy could help guide future clinical decisions and could help identify patients at risk for worse outcomes.

Reference

Calverley PMA, Anzueto AR, Dusser D, et al. Treatment of exacerbations as a predictor of subsequent outcomes in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:1297-1308. doi.org/10.2147/COPD.S153631.