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. 2021 Jun 23;30(160):210075.
doi: 10.1183/16000617.0075-2021. Print 2021 Jun 30.

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD

Marc Miravitlles  1   2 , Ariadna Auladell-Rispau  3   2 , Mònica Monteagudo  4   5 , Juan Carlos Vázquez-Niebla  3 , Jibril Mohammed  6 , Alexa Nuñez  7 , Gerard Urrútia  3
Affiliations

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD

Marc Miravitlles et al. Eur Respir Rev. .

Abstract

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.

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Conflict of interest statement

Conflict of interest: M. Miravitlles reports speakers fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Zambon, Sandoz, CSL Behring, Grifols and Novartis; consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Kamada, TEVA, Sanofi, pH Pharma, Novartis and Grifols; and research grants from GlaxoSmithKline and Grifols, outside the submitted work. Conflict of interest: A. Auladell-Rispau has nothing to disclose. Conflict of interest: M. Monteagudo has nothing to disclose. Conflict of interest: J.C. Vázquez-Niebla has nothing to disclose. Conflict of interest: J. Mohammed reports a grant from the European Respiratory Society (ERS Fellowship in Guidelines Methodology), outside the submitted work. Conflict of interest: A. Nuñez has nothing to disclose. Conflict of interest: G. Urrútia has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Pooled risk ratios for pneumonia (Mantel-Haenszel, random-effects model). ICS: inhaled corticosteroid.
FIGURE 2
FIGURE 2
Pooled risk ratios for fractures (Mantel-Haenszel, random-effects model). ICS: inhaled corticosteroid.
FIGURE 3
FIGURE 3
Pooled risk ratios for diabetes (Mantel-Haenszel, random-effects model) in randomised clinical trials. Vestbo [14] and Dransfield [25] measured effects on glucose levels; Vestbo [16] and Rabe [34] measured hyperglycaemia/new-onset diabetes mellitus. ICS: inhaled corticosteroid.
FIGURE 4
FIGURE 4
Pooled hazard ratios for diabetes (inverse variance method, random-effects model) in cohort studies. Data from Saeed [64] refer exclusively to patients treated with low-dose inhaled corticosteroids (ICS).
See this image and copyright information in PMC

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