PURPOSE: To assess efficacy and safety of etanercept 25 mg twice weekly (BIW) in subjects with severe persistent asthma, uncontrolled despite high-dose ICS (GINA 2006).
METHODS: A randomized,double blind, placebo-controlled, 12-week study. Eligible subjects were randomly assigned to etanercept or placebo. Evaluations were performed at baseline, weeks 2, 4, 8, and 12, and follow-up. The primary efficacy endpoint was change from baseline in FEV1 % predicted at week 12. Efficacy was analysed using the ITT population; LOCF accounted for missing data.
RESULTS: In addition to ICS, almost 90% of subjects were receiving long-acting beta2 agonists and 15% were receiving systemic corticosteroids. Of 132 subjects enrolled, 68 were randomly assigned to etanercept and 64 to placebo. 131 subjects received ≥1 dose of test article. 19 withdrew, 11 because of an adverse event. There were no statistically significant differences between etanercept and placebo in any of the efficacy endpoints (Table). However, etanercept resulted in a twofold increase in PC20 compared with no change with placebo. In posthoc analyses: 1.) The effect of etanercept versus placebo on change in FEV1 % predicted was similar regardless of whether patients received concomitant oral steroids or not; adjusted mean differences at 12 weeks were 0.8 (1.8; p=0.6433) and 4.1 (6.7; p=0.5432) respectively; 2.) Patients in the lowest tertile of lung function (FEV % predicted ≤;60%) at study entry did not show a significantly greater response than those with FEV % predicted >60%; adjusted mean difference were 1.6 (3.2; p=0626) and 0.6 (2.3; p=0.809) respectively. Injection site reactions (25 [37%] for etanercept and 7 [11%], p=0.0009 for placebo) were the only TEAES that were significantly different between the groups. Infections were experienced by 30 (44.1%) and 34 (54.0%) patients receiving etanercept and placebo respectively (p=0.296).
CONCLUSION: Etanercept 25 mg BIW did not demonstrate efficacy in the treatment of severe persistent asthma.
CLINICAL IMPLICATIONS: Although well tolerated, inhibition of TNF as a treatment modality did not appear to result in clinical benefit for patients with severe asthma.
DISCLOSURE: Stephen Holgate, No Product/Research Disclosure Information; Grant monies (from industry related sources) Dr Nelson receives grant support from Schering-Plough, Behringer, IVAX, Novartis, MediciNova, Clinical Therpeutics, Wyeth, Sepracor, Altana, Genentech, and GenTel. Dr. Pavord and Dr. Busse received grant support from Wyeth for this study; Employee Drs Paolozzi, McDermott, and Wajdula are employees of Wyeth; Consultant fee, speaker bureau, advisory committee, etc. Dr. Noonan was also a consultant for Wyeth relating to patient availability for trials. Dr Nelson is a consultant for Genentech/Novartis, Dey Laboratories, Curalogic, Dynavax Technologies, GlaxoSmithKline, Johnson and Johnson, Schering-Plough (Integrated Therapeutics Group), Astellas, Merck, Altana; Other Dr. Nelson is a member of the Glaxo SmithKline and Astra Zeneca Speakers Bureaus.