Comparison of PEF vs. FEV1 Endpoints in Trials with Tiotropium in Adults and Adolescents with Moderate or Severe Symptomatic Asthma

RATIONALE: In adults and adolescents FEV₁ is generally viewed as the preferred lung function assessment in asthma clinical trials. PEF was assessed as an alternative endpoint.

METHODS: FEV₁ and PEF outcomes from 7 trials with tiotropium Respimat^® add-on to ICS ± additional controllers were compared. Change from baseline in peak FEV_1(0–3h), trough FEV₁ and PEF_am/pm with tiotropium 5µg, 2.5µg and placebo, delivered by Respimat^® (2 puffs once daily), were analyzed from studies in patients with symptomatic asthma (adults: GraziaTinA-asthma^®, MezzoTinA-asthma^® and PrimoTinA-asthma^®; 12–17-year-olds: PensieTinA-asthma^® and RubaTinA-asthma^®). Correlation of in-clinic and weekly mean home measurements (AM3^® Home Spirometer and eDiary) of FEV₁ and PEF was also analyzed post hoc.

RESULTS: Improvements in both measures of lung function were seen in all studies with tiotropium Respimat^®: FEV_1(0–3h), 90–185mL and 111–223mL with 5µg and 2.5µg, respectively; and PEF_am, 15.8–25.6L/min and 9.7–26.3L/min with 5µg and 2.5µg, respectively. PEF appeared better able to identify tiotropium dose-response relationships. Measurements at home versus those in-clinic correlated better for PEF (intraclass correlation coefficient [ICC] 0.724–0.839) than for FEV₁ (ICC 0.575–0.818), at Week 12 or 24, depending on the study, indicating that home assessed PEF as an endpoint may give additional information over and above FEV₁.

CONCLUSIONS: FEV₁ and PEF both improved with tiotropium added to ICS ± other controllers versus placebo in all studies. However, home PEF measurements may have certain advantages over home FEV₁ measurements such as identification of dose ordering, ease of use and increasing convenience for the study subject.