①Corren等人(本刊9月22期)报道，在哮喘患者中，使用利布利克珠单抗治疗与肺功能的改善有关，而在治疗前血清骨膜蛋白水平高或呼出的一氧化氮(FENO)比例高的的患者中，改善效果显著。②作者合理地强调了骨膜蛋白，因为它的在不同病人之间的差异较小，但同时，他们提出了一个重要的问题：个体患者在基线时，骨膜蛋白和呼出的一氧化氮(FENO)比例之间的关系是什么? 利布利克珠单抗治疗12周后, 高FENO水平组1秒用力呼气量(FEV1)提高8.6%,与安慰剂相比(P = 0.02),高骨膜蛋白水平组提高8.2%,与安慰剂相比(P = 0.03)。③在治疗24周时，高FENO水平组FEV1的 改善比高骨膜蛋白组大 40% (5.9%比4.2%)(利布利克珠单抗治疗组与安慰剂组相比，高FENO 组，P = 0.09,高骨膜蛋白组 P = 0.26)(见补充附录表S4, 在NEJM.org可获得Corren等人全文)。④这些数据表明，一些同时具有低骨膜蛋白水平和高FENO水平的患者可能与骨膜蛋白水平高的患者一样受益于利布利珠单抗治疗。如果是这样，这将增加被认为可能对利布利单抗有应答的患者数量。研究骨膜蛋白和FENO之间的关系也可能为了解利布利克珠单抗的作用机制提供线索。
T h e NEW ENGLAND JOUR NAL o f MEDICINE
N ENGL J MED 365;25 NEJM.ORG DECEMBER 22, 2011
Corren et al. (Sept. 22 issue)1 report that treatment with lebrikizumab was associated with improved lung function in patients with asthma, and that improvement wasgreater in patients with high pretreatment levels of serum periostin or of the fraction of exhaled nitric oxide (FENO). The authors justifiably emphasize periostin because of its lower intra-patient variability, but in doing so, they raise an important question: what is the relationship between periostin and FENO at baseline in individual patients? After 12 weeks of lebrikizumab therapy, forced expiratory volume in 1 second (FEV1) improved by 8.6 percentage points in the group with high FENO levels, as compared with placebo (P = 0.02), and by 8.2 percentage points in the group with high periostin levels, as compared with placebo (P = 0.03). At 24 weeks, improvement in FEV1 was 40% greater in the FENO-high group than in the periostin-high group (5.9% vs. 4.2%) (P = 0.09 in the FENO-high group and P = 0.26 in the periostin-high group for the comparison of lebrikizumab with placebo) (see Table S4 in the Supplementary Appendix, available with the full text of the article by Corren et al. at NEJM.org). These data suggest that some patients who have both low-periostin levels and high FENO levels may benefit from lebrikizumab treatment as much as patients in the periostin-high group do. If so, this would increase the number of patients considered likely to respond to lebrikizumab. Investigating the re-lationship between periostin and FENO may also provide insight into the mechanism of action of lebrikizumab.
Benjamin Zeskind, Ph.D.