BACKGROUND

CompEx Asthma, a novel composite end-point combining severe exacerbations (SevEx) with asthma-worsening events, was recently developed. Further characterisation of CompEx Asthma is needed to illustrate the applicability of this end-point. The objective was to evaluate CompEx Asthma as a rate end-point to determine how seasonal and geographical factors impact this novel outcome.

METHODS

Seven 24-56-week randomised controlled trials of budesonide/formoterol (BUD/FORM) and benralizumab were analysed. Annualised event rates (AERs) and treatment effects (hazard ratio (HR)) were analysed with Poisson and Andersen-Gill models, respectively. Seasonality was analysed by month and five geographical regions were evaluated.

RESULTS

The studies included 10 815 patients (63% female, mean age 42-49 years). CompEx Asthma AER mirrored seasonal variations in SevEx AER. CompEx Asthma AERs were higher SevEx in BUD/FORM and benralizumab trials (range 2.7-4.5-fold and 1.3-2.0-fold increase, respectively) and were less variable SevEx between regions (ratios of greatest:smallest AERs: 1.36 for CompEx 2.28 for SevEx (BUD/FORM); 1.81 for CompEx 2.22 for SevEx (benralizumab)). Treatment effects for CompEx Asthma and SevEx were generally similar across regions and months. However, in Eastern Europe, where SevEx rates were lowest, treatment effect was greater with CompEx Asthma SevEx, reaching statistical significance in the benralizumab studies (HR (95% CI): 0.67 (0.53-0.85) 0.87 (0.65-1.15)).

CONCLUSION

This study confirmed the reliability of CompEx Asthma as a rate end-point and allowed detection of variations in seasonal SevEx rates, reduction of variation in rates across regions and potential greater sensitivity to treatment effects.