Interclass Difference in Pneumonia Risk in COPD Patients Initiating Fixed Dose Inhaled Treatment Containing Extrafine Particle Beclometasone versus Fine Particle Fluticasone

Abstract

Background: Inhaled corticosteroids (ICS) afford therapeutic benefits in some COPD patients, but their widespread use is cautioned due to an increased risk of developing pneumonia. Subclass variations exist, and the risk profile differs for individual ICS. Formulation particle size has been identified as a potential effect modifier. The present study compared the risk of pneumonia among new COPD users of fixed-dose combination inhalers containing fine-particle fluticasone (fp-FDC-F) versus extrafine particle beclometasone (ef-FDC-BDP). Methods: A propensity matched historical cohort study was conducted using data from the Optimum Patient Care Research Database. COPD patients aged ≥40 years with ≥1 year of continuous medical data who initiated fp-FDC-F or ef-FDC-BDP were compared. The primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions. Results: A total of 13,316 patients were matched. Initiation of fp-FDC-F (mean dosage furoate 99 µg; propionate 710 µg) was associated with an increased risk of pneumonia versus ef-FDC-BDP (mean beclometasone dose 395 µg), irrespective of definition (sensitive HR 1.38 95% CI 1.14-1.68; specific HR 1.31 95% CI 1.05-1.62). Conclusion:In the current investigation, we found that in comparison to extrafine beclomethasone, commencing a formulation containing fluticasone is associated with an increased risk of developing pneumonia. These observations support the idea that not all ICS are equal in their adverse effects and subclass variations exist and should be carefully considered in the treatment choice.

What have we learnt from real‐life research in asthma and COPD? Standards and novel designs for the future

“… Do fine‐particle fluticasone‐containing ICS formulations have implications in the clinical management of patients with COPD? In real‐life research, patients treated with a fluticasone‐containing ICS formulation were found to have an increased risk of pneumonia, in comparison to patients treated with extrafine beclomethasone 7 . The study's findings emphasize the need for clinicians to be aware of fine‐particle fluticasone‐containing ICS formulations and their different adverse effects when selecting treatments 7 …”

“…Much like registries, EMRs and databases such as the Optimum Patient Care Research Database (OPCRD) and Clinical Practice Research Datalink (CPRD) can also add value to the breadth of research on severe asthma and COPD. The OPCRD database has a median follow‐up period of 13 years (with diagnostic information from birth for many patients), offering increased power to study rare adverse events such as pneumonia which RCTs are less able to do 7 . Here are some previously unanswered questions that EMR‐based observational studies have now answered: Does lung function decline more rapidly in asthmatics with more frequent exacerbations?…”

“…7 The study's findings emphasize the need for clinicians to be aware of fine-particle fluticasone-containing ICS formulations and their different adverse effects when selecting treatments. 7 Along with registries and observational studies, real-life research also encompasses pragmatic trials. Here is an example of a previously unanswered research question addressed by a pragmatic trial:…”

“…The OPCRD database has a median follow-up period of 13 years (with diagnostic information from birth for many patients), offering increased power to study rare adverse events such as pneumonia which RCTs are less able to do. 7 Here are some previously unanswered questions that EMR-based observational studies have now answered:…”

Impulse Oscillometry, Small Airways Disease, and Extra-Fine Formulations in Asthma and Chronic Obstructive Pulmonary Disease: Windows for New Opportunities

“…28 In particular, the risk of pneumonia changes with ICS subclass and is lower when using extra-fine ICS at lower ICS doses. [29][30][31] Nonetheless the topic is still subject to debate; a network meta-analysis comparing nine combinations of ICS/LABA/LAMA in COPD found significantly lower pneumonia infections only with the fluticasone propionate (FP)/ glycopyrrolate/salmeterol (SAL). 31 Further evidence on the relationship between distribution to small airways and better clinical control is provided by a recent study specifically assessing the efficacy of an extra-fine formulation of beclomethasone dipropionate/ formoterol fumarate (BDP/FF) 100/6 µg b.i.d in COPD patients with SAD.…”