Relationship Between “Morning Dipping” in Peak Expiratory Flow (PEF) or Peak Expiratory Flow Variability (PEFV) and Study Withdrawals: Post Hoc Analysis of a Randomized 12-Week Study in Patients with Moderate to Severe Asthma

Abstract

RATIONALE: Early study discontinuations may indicate poor asthma control. We assessed the relationship between morning PEF dips or PEFV and study discontinuation due to an asthma event based on prespecified criteria (lung function, rescue medication use, awakenings, need for healthcare utilization).METHODS: This post hoc analysis of a randomized, double-blind 12-week study (NCT00652002 [Drugs. 2006;66:2235-54]) included moderate-severe persistent asthma patients receiving placebo and as-needed albuterol with ≥2 weeks of observation (first 2 weeks censored to wash out any inhaled corticosteroid run-in effects). Patients recorded morning and evening PEF daily via e-diary. Morning dipping was defined as percent decrease in morning versus evening PEF, averaged over the treatment period. PEFV was calculated as (maximal PEF-minimum PEF)/mean PEF over the treatment period. Associations between percent morning dipping or PEFV and study withdrawals were assessed.RESULTS: Of 125 placebo patients, 70 were included in this analysis, of whom 27% did not demonstrate morning dipping as defined; 64% and 9% had morning dipping <7.5% and ≥7.5%, respectively. Most patients (69%) had PEFV <7.5%. Compared with completers (n=47 [67% of patients]), patients with early withdrawal (n=23 [33% of patients]) had twice the mean percent morning dipping (3.9% vs 1.7%) and PEFV (10.4% vs 5.2%). The most commonly met discontinuation criterion was decreased forced expiratory volume in 1 second.CONCLUSIONS: Increased morning dipping and PEFV was associated with premature discontinuation from the placebo arm of a clinical trial due to predefined asthma event. These findings support the value of morning dipping and PEFV as relevant asthma control indicators. RATIONALE: Early study discontinuations may indicate poor asthma control. We assessed the relationship between morning PEF dips or PEFV and study discontinuation due to an asthma event based on prespecified criteria (lung function, rescue medication use, awakenings, need for healthcare utilization). METHODS: This post hoc analysis of a randomized, double-blind 12-week study (NCT00652002 [Drugs. 2006;66:2235-54]) included moderate-severe persistent asthma patients receiving placebo and as-needed albuterol with ≥2 weeks of observation (first 2 weeks censored to wash out any inhaled corticosteroid run-in effects). Patients recorded morning and evening PEF daily via e-diary. Morning dipping was defined as percent decrease in morning versus evening PEF, averaged over the treatment period. PEFV was calculated as (maximal PEF-minimum PEF)/mean PEF over the treatment period. Associations between percent morning dipping or PEFV and study withdrawals were assessed. RESULTS: Of 125 placebo patients, 70 were included in this analysis, of whom 27% did not demonstrate morning dipping as defined; 64% and 9% had morning dipping <7.5% and ≥7.5%, respectively. Most patients (69%) had PEFV <7.5%. Compared with completers (n=47 [67% of patients]), patients with early withdrawal (n=23 [33% of patients]) had twice the mean percent morning dipping (3.9% vs 1.7%) and PEFV (10.4% vs 5.2%). The most commonly met discontinuation criterion was decreased forced expiratory volume in 1 second. CONCLUSIONS: Increased morning dipping and PEFV was associated with premature discontinuation from the placebo arm of a clinical trial due to predefined asthma event. These findings support the value of morning dipping and PEFV as relevant asthma control indicators.