Comparison of PEF vs. FEV1 Endpoints in Trials with Tiotropium in Adults and Adolescents with Moderate or Severe Symptomatic Asthma
Monday, March 5, 2018
South Hall A2 (Convention Center)
David M.G. Halpin, MD, J Mark FitzGerald, FRCPC, Michael Engel, MD, Petra Moroni-Zentgraf, MD, Ralf Sigmund, Eli O. Meltzer, MD, Thomas B. Casale, MD FAAAAI
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 FEV1(0–3h), trough FEV1 and PEFam/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®: FEV1(0–3h), 90–185mL and 111–223mL with 5µg and 2.5µg, respectively; and PEFam, 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.