ICS use in COPD, asthma does not affect COVID-19-related mortality

Regular use of inhaled corticosteroids (ICS) for the treatment of chronic obstructive pulmonary disease (COPD) or asthma does not appear to affect COVID-19-related mortality, an observational study from England showed.

“[O]ur findings do not provide any strong support for a protective effect from ICS use in these populations, as has been previously hypothesized might exist,” the researchers pointed out. “[N]o evidence supports that patients should alter their ICS therapies during the ongoing pandemic.”

Primary care electronic health records of patients with COPD (n=148,557) or asthma (n=818,490) were linked with death data from the Office for National Statistics. Eligibility criteria for patients with COPD was age ≥35 years, current or former smoker, and prescribed ICS plus LABA or LABA–LAMA* within 4 months of the onset of follow-up (index date). Eligibility criteria for patients with asthma was age ≥18 years, diagnosed with asthma within 3 years of the index date, and treated with ICS or SABA* only within 4 months of the index date.

There were 429 and 529 COVID-19-related deaths in the COPD and asthma cohort, respectively. [Lancet Respir Med 2020;8:1106-1120]

Among patients with COPD, those prescribed ICS combinations had a higher risk of COVID-19-related mortality compared with those prescribed LABA–LAMA (adjusted hazard ratio [adjHR], 1.39, 95 percent confidence interval [CI], 1.10–1.76).

Among patients with asthma, COVID-19-related mortality risk was higher with high-dose ICS vs SABA only (adjHR, 1.55, 95 percent CI, 1.10–2.18), a risk not noted among those prescribed low- or medium-dose ICS (adjHR, 1.14, 95 percent CI, 0.85–1.54).

However, absolute mortality risk was very low, with estimated cumulative COVID-19-related mortality 0.09 percent higher with ICS vs LABA–LAMA and 0.03 percent higher with high-dose ICS vs SABA in the COPD and asthma cohorts, respectively, the researchers noted.

“The observed harmful associations between ICS prescription and COVID-19-related death could be readily explained by confounding due to underlying health differences between people prescribed ICS and those using other medications for asthma and COPD … rather than representing a causally harmful effect of ICS,” they added.

This lines up with sensitivity analysis which demonstrated a greater COVID-19-related mortality risk in the COPD cohort among those prescribed triple therapy (ICS–LABA–LAMA) compared with dual therapy (ICS–LABA; adjHR, 1.43, 95 percent CI, 1.12–1.83 and adjHR, 1.29, 95 percent CI, 0.96–1.74), where ICS content was comparable between the two regimens.

Non-COVID-19-related mortality risk was elevated among patients prescribed ICS vs LABA–LAMA in the COPD cohort (adjHR, 1.23, 95 percent CI, 1.08–1.40), though not with ICS (regardless of dose) vs SABA in the asthma cohort.

This suggests there were other unavailable markers of disease severity in the COPD cohort, the researchers said.

The current stand

“[O]ur results should ... provide reassurance to patients relying on ICS that the use of these medications has not put them at undue risk of negative outcomes during the ongoing pandemic,” said the researchers.

However, they acknowledged that the use of pre-lockdown prescription data may not have reflected treatment adherence, leading to potential “exposure misclassification.”

“Overall, the analysis … does not provide definitive answers that patients and clinicians need … [and] does not completely resolve whether regular ICS therapy for asthma or COPD either decreases or increases risk of death from COVID-19,” commented Professors Dave Singh and David Halpin from the University of Manchester and University of Exeter, UK, respectively. [Lancet Respir Med 2020;8:1065-1066]

Accounting for clinical factors that may have influenced therapy choice may have produced different results, they said.

“This finding is in contrast with the very real harm patients requiring ICS therapy for their asthma or COPD might be at risk if they stop treatment because of unfounded concerns related to their effects in COVID-19.” Pending more conclusive findings, patients with asthma or COPD who are stable while on ICS should continue their treatment, they said.