Asthma's complex and protean inflammatory processes vary between individuals, some of whom have elevated levels of interleukin-13 despite maximal treatment with inhaled steroids. IL-13 prompts airway epithelial cells to secrete periostin, which acts on fibroblasts and may contribute to airway remodeling in asthma. Lebrikizumab is a monoclonal antibody inhibiting IL-13.
Corren et al used a "dynamic randomization scheme" to create placebo / lebrikizumab groups among 219 patients in a 1:1 ratio. Patients had uncontrolled asthma on high dose steroids, with FEV1 40-80% predicted with a bronchodilator response. Lebrikizumab was given in 250 mg subcutaneous injection once a month.
The "scheme" involved stratifying the patients prior to randomization according to predicted IL-13 levels (using IgE and blood eosinophils as a surrogate, since IL-13 is hard to measure). Randomization was then "balanced" to prevent the chance excess of patients with the high-IL-13 profile in the placebo group, which investigators likely feared would falsely diminish the treatment effect. (Midway through, they realized they could measure serum periostin, which was more predictive of response to lebrikizumab than the other surrogate measures.)
The drug improved spirometric parameters: prebronchodilator FEV1 increased by 5.5% in the treatment group (over placebo) at 12 weeks (1' endpoint). The patients with high periostin had an 8% increase in FEV1 over placebo (14% vs. 5%); the low-periostins, only 1.6%. However, lebrikizumab did not improve asthma scores or exacerbation rates (2' endpoints), even when considering only the high-periostin group.
"Musculoskeletal events" occurred in 13% of the lebrikizumab group, compared to 5% of placebo (p<0.05). They looked mild (tendinitis, bursitis, arthralgia, etc).
Genentech paid for the study, and "the study protocol was designed, written, and edited, and the data were stored and analyzed, by employees of [Genentech] ... One clinical investigator and one industry author wrote the first draft of the manuscript ... A third party was hired by [Genentech] to provide assistance with the writing of the manuscript."
By the way, if I misspelled lebrikizumab anywhere here, I'm not sorry: that's what you get for naming your drug that.
Corren J et al. Lebrikizumab Treatment in Adults with Asthma. N Engl J Med 2011;August 3 epub. FREE FULL TEXT