Rapid Lung Function Improvement with Lebrikizumab in Patients with Uncontrolled Asthma
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Jonathan Corren, MD, Nicola A. Hanania, MD, Phillip E. Korenblat, MD, FAAAAI, Julie K. Olssen, MD, MS, Nikhil Kamath, MD, Sarah Gray, PhD, Nicolas Martin, Cecile T.J. Holweg, PhD, John G. Matthews, MB, BS, MRSCP, PhD, Susan L. Limb, MD, Stephan Korom
Rationale: Interleukin-13 is a pivotal cytokine within Type 2 asthma pathophysiology, driving airway hyperresponsiveness, mucus production and remodeling. Here, we assess the improvement in FEV1 with lebrikizumab therapy. 

Methods: We conducted a pooled analysis of three trials (NCT00930163/NCT01545440/NCT01545453) including 565 patients with moderate-to-severe uncontrolled asthma receiving ICS (200–2000 µg/day fluticasone propionate or equivalent), ≥1 additional controller (>90% LABA), pre-bronchodilator FEV1 40–80% predicted and ≥12% FEV1 reversibility. Lebrikizumab (125 or 250 mg) was administered subcutaneously every 4 weeks to 337 patients, and 228 patients received placebo. Change in FEV1 at Weeks 1 and 12 was assessed according to baseline serum periostin level (≥50 ng/mL vs. <50 ng/mL).

Results: In patients with baseline serum periostin levels ≥50 ng/mL, the mean (SD) absolute increase in FEV1 from baseline was 208 (361) mL in lebrikizumab-treated patients versus 67 (262) mL with placebo at Week 1. Week 12 FEV1 improvement from baseline was 292 (390) mL in lebrikizumab versus 94 (280) mL in placebo-treated patients. Lebrikizumab-treated patients with serum periostin <50 ng/mL at baseline showed a smaller FEV1 improvement at Weeks 1 and 12 of 143 (326) mL and 180 (298) mL, respectively versus placebo 86 (266) mL and 106 (293) mL. 

Conclusions: In patients with moderate-to-severe uncontrolled asthma with high serum periostin, a single dose of lebrikizumab led to a rapid, clinically meaningful increase in FEV1 within 1 week that was sustained to Week 12. These data illustrate the efficacy of lebrikizumab on improving airway function in patients with moderate-to-severe Type 2-mediated asthma.