PURPOSE:Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone).METHODS:This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change.RESULTS:Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) μg/day and 500 (250-500) μg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide.CONCLUSIONS:In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.

Background: Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre-post historical database study to investigate asthma-related outcomes by treatment. Methods: We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Results: Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fineparticle ICS. The IPTW and propensity score-based methods retained more patients (96%-100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. Conclusion: We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations.

Background: Asthma guidelines recommend extrafine (EF)-ICS be prescribed at the same dose as fluticasone and half dose of beclomethasone [standard-particle (SP)-ICS]. Aim: To compare real-life prescribed doses of ciclesonide (EF-ICS) vs SP-ICS and evaluate their effect on treatment outcomes for patients receiving asthma therapy in The Netherlands. Methods: Pharmacy/hospital records from the PHARMO Database Network (20% of the Dutch population) were collected over 1-year before and 1-year after patients (12-60 years, not on long-acting muscarinic-antagonists) initiated EF or SP-ICS therapy. Initial ICS doses and adjusted rate/odds ratios (RR/OR) of severe exacerbations (hospital admissions/acute oral steroids), changing therapy (additional therapy/increased ICS dose) and increasing short-acting β2-agonists (SABA) doses (categorised) were compared between treatment groups. To avoid bias by severity, patients were exact-matched on key baseline differences. Results: The table shows RR/OR for EF vs SP-ICS matched patients (median age 45 years, 35% males in each group). Median prescribed doses were 120 vs 500mcg for EF (actual dose) vs SP-ICS (FP equivalents). Conclusions: For matched patients ciclesonide was prescribed at one-third of the dose of SP-ICS, yet patients prescribed ciclesonide had lower exacerbation rates and lower odds of changing therapy and receiving higher SABA doses.