Withdrawing inhaled corticosteroids does not appear to expedite FEV1 declines in COPD

Across cohorts of patients with COPD, withdrawing inhaled corticosteroids from triple therapy resulted in similar FEV₁ declines as remaining on triple therapy, according to a study published in Annals of the American Thoracic Society.

However, researchers observed larger declines in FEV₁ related to inhaled corticosteroids (ICS) withdrawal specifically in a general cohort of primary care patients with COPD.

“This suggests that in a general population, there may be a protective effect of ICS on lung function decline; however, although this result was statistically significant, the difference of 3.8 ml [per] year between the two exposures is not likely to be clinically significant,” Hannah R. Whittaker, PhD, MSc, research associate in epidemiology/medical statistics from Imperial College London, and colleagues wrote.

Whittaker and colleagues analyzed 99,535 adults with COPD and on triple therapy (ICS/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) for at least 4 months to determine how withdrawal from ICS was related to FEV₁ decline.

Previously, the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) randomized control trial found that ICS withdrawal was linked to greater FEV₁ decline than staying on triple therapy. Eligibility criteria for the WISDOM trial included age 40 years or older, a FEV₁ percent predicted less than 50% and having an exacerbation event within the period from 1 year before to 6 weeks before follow-up.

In order to analyze FEV₁ decline rates across various groups of patients with COPD, researchers constructed three cohorts: Patients who met eligibility criteria for the WISDOM trial (n = 6,008), primary care patients with COPD aged 35 or older from the general population (n = 60,645) and patients with comorbidities that would have excluded them from participating in the WISDOM trial (n = 32,882). Researchers obtained data on their patient population from electronic health care records in England and divided them according to whether they stayed on triple therapy or withdrew from ICS in follow-up.

Researchers evaluated the relationship between ICS withdrawal and decreases in FEV₁ through mixed linear regression adjusted for baseline characteristics.

Overall, results showed no differences in FEV₁ decline rates between ICS withdrawal and remaining on triple therapy for both cohorts of patients hypothetically included and excluded from the WISDOM trial in adjusted analysis.

Of the patients eligible for the trial, ICS withdrawal patients (n = 538; 8.9%) had an adjusted mean FEV₁ decline rate of –7.8 ml/year (95% CI, –19.7 to 4.1) compared with –15.2 ml/year (95% CI, –18.7 to –11.8) among the triple therapy patients (n = 5,470; 91.1%).

Similarly, patients not eligible for WISDOM who withdrew from ICS (n = 3,581; 10.9%) had an adjusted mean FEV₁ decline rate of –31.3 ml/year (95% CI, –35 to –27.5) compared with –29.4 ml/year (95% CI, –30.8 to –28.1) among patients still on triple therapy (n = 29,301; 89.1%).

The only cohort that showed patients who withdrew from ICS to have a larger decline in FEV₁ was the one made up of general patients with COPD. ICS withdrawal patients (n = 6,974; 11.5%) had an adjusted mean decline rate of –36.4 ml/year (95% CI, –39.4 to –33.4) whereas triple therapy patients (n = 53,671; 88.5%) had a mean decline rate of –32.6 ml/year (95% CI, –33.6 to –31.5; P = .01).

“Patients with COPD who are seen in clinical practice may not adhere to their treatments and are often different in terms of comorbidities and disease severity from those included in [randomized control trials] such as the WISDOM trial,” Whittaker and colleagues wrote. “Further observational studies or pragmatic trials should be performed to better understand the relationship between ICS withdrawal and the rate of FEV₁ decline in more generalizable patients with COPD.”