Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Abstract

Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial

“…Furthermore, when disease severity was categorically graded (mild, moderate and severe) based on a linear regression curve of WCS plotted against RL, 27 a reduction in WCS of 30% ensured an improvement in at least one severity grade; namely, moderate to mild and severe to moderate (except horses which were included with a total score of ≥21). Moreover, the magnitude of change in RL underpinning the change in severity grade assessed in the dose finding studies 27 exceeded the lower limit of 0.63cmH2O/L/s (95% CI 0.33‐0.94) recently reported by Calzetta et al as the minimal change in RL which can be appreciated by a meaningful improvement in clinical signs following bronchodilator treatment of severe equine asthma 33 …”

“…Moreover, the magnitude of change in RL underpinning the change in severity grade assessed in the dose finding studies 27 exceeded the lower limit of 0.63cm-H2O/L/s (95% CI 0.33-0.94) recently reported by Calzetta et al as the minimal change in RL which can be appreciated by a meaningful improvement in clinical signs following bronchodilator treatment of severe equine asthma. 33 Importantly, the clinical relevance of the favourable response to ciclesonide administration was further substantiated by the owner's perception of change in their horse's QoL; indeed, the percentage of ciclesonide-treated horses considered to have an improved QoL largely mirrored that of ciclesonide-treated horses with a minimum 30% improvement in WCS.…”

“…Moreover, the magnitude of change in RL underpinning the change in severity grade assessed in the dose finding studies 27 exceeded the lower limit of 0.63cmH2O/L/s (95% CI 0.33‐0.94) recently reported by Calzetta et al as the minimal change in RL which can be appreciated by a meaningful improvement in clinical signs following bronchodilator treatment of severe equine asthma. 33 …”

Adding a Second Bronchodilator in COPD: A Meta-Analysis on the Risk of Specific Cardiovascular Serious Adverse Events of Tiotropium/Olodaterol Fixed-Dose Combination

“…Moreover, since the follow-up duration was not consistent across the RCTs, the data have been normalized as a function of person-year [26,27]. This method, supported by the Cochrane Collaboration and successfully used in recent meta-analyses [14,[19][20][21] involves the conversion of the measures into a common metric (events per person-time) prior to meta-analyzing the data, leading to improved estimates of effect, precision, and clinical interpretability of results [19,20]. Subset analyses were performed with regard to the effect of the class of monocomponents included in the FDC (LABA or LAMA).…”

“…The test for heterogeneity (I 2 ) was performed for primary endpoint to quantify the bias introduced by between-study dissimilarity, as previously reported [19], and low, moderate, and high heterogeneity was assigned for I 2 values of '25%, '50%, and '75%, respectively [20].…”