<p>Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies</p>

Abstract

Background Inhaled corticosteroids (ICS) are widely used and recommended to treat chronic obstructive pulmonary disease (COPD). While generally considered safe, several studies demonstrated an increased risk of pneumonia with the use of ICS in COPD patients. Although all ICS indicated for COPD carry the class labeling warning of increased pneumonia risk, evidence suggests an intraclass difference in the risk of pneumonia between inhaled budesonide and fluticasone. To date, systematic reviews of direct-comparison studies have not been performed to assess if an intraclass difference exists. Research Question This review investigated whether there is an intraclass difference in risk of pneumonia between inhaled fluticasone and budesonide, the 2 most commonly used ICS in COPD. Study Design and Methods A search of the medical literature was conducted in PubMed and Embase for the time period of 01/01/69–05/31/19. The search strategy combined terms that defined the patient/disease type, exposures, outcome, and the study/publication type. Descriptive and comparative statistics reported for fluticasone- and budesonide-containing products in each study, including data for pneumonia event subgroups, were extracted and reported by dose, seriousness, or practice setting. Controlled clinical trials and observational studies meeting the inclusion criteria were assessed for methodologic quality by using the appropriate tool from the list of study quality assessment tools developed by the National Institutes of Health. Results The summary relative risk (RR) ratio across 5 included studies (57,199 patients) was 1.13 (95% CI: 1.09–1.19), representing a 13.5% increased risk of pneumonia among fluticasone users compared to budesonide users. Similarly, summary RR ratio for serious pneumonia implied a 14.4% increased risk of serious pneumonia among fluticasone users compared to budesonide users (pooled RR: 1.14; 95% CI: 1.09–1.20). Interpretation There is likely a clinically important intraclass difference in the risk of pneumonia between fluticasone- and budesonide-containing inhaled medications in COPD.

Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease

“…Furthermore, there may be an increased risk for pneumonia in patients with COPD who use ICS. This risk however strongly depends on the corticosteroid component and the device [ 69 ]. COPD patients with predominantly eosinophilic airway inflammation [ 27 ] may gain the most benefit from ICS [ 31 , 70 ].…”

Reply to: “Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies” [Letter]

“…These are different compounds with different molecular structures, potency and dosages. Of the six fluticasone studies discussed, 1 five investigated FP, whereas one (Lipson et al) investigated FF. These drugs need to be analysed separately.…”

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We read with interest the article by Lodise et al 1 The analysis is fundamentally flawed. The authors conclude that there is a greater risk of pneumonia with fluticasone compared with budesonide (BUD).

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“…At 24 weeks there was a higher rate of pneumonia with FF/umeclidinium/vilanterol (FF/UMEC/VI) compared with BUD/ formoterol (BUD/FOR), but at 52 weeks there was no difference, which the authors fail to mention. 1 When Lodise et al was published they will have been aware of the results of the ETHOS study. 4 The ETHOS and IMPACT studies recruited similar groups of patients with symptomatic COPD and a history of exacerbations, but defined pneumonia in different ways, which may result in different absolute pneumonia rates.…”

Response to the Letter to the Editor Regarding “Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies” [Response to Letter]

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We read with interest the remarks from Barnes et al regarding our recently published work (Lodise et al 2020;15:2889-2900). 1 They raise some observations based on several flawed arguments that we would be glad to address in turn.First, Barnes et al suggest that as fluticasone furoate (FF) and fluticasone propionate (FP) are molecularly distinct compounds, they should be analyzed separately. However, no head-to-head clinical trial has conclusively demonstrated a lower/different pneumonia risk with FF versus FP, and the grouping of FF and FP in our analysis is consistent with the approach taken by previous independent investigations, including by the European Medicines Agency (EMA, per the 2016 EMA Pharmacovigilance Risk Assessment Committee) and a recent meta-analysis.

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