Que Y-A, Lazar H, Wolff M, François B, Laterre P-F, Mercier E, Garbino J, Pagani J-L, Revelly J-P, Mus E, Perez A, Tamm M, Rouby J-J, Lu Q, Chastre J, Eggimann P
Adult Critical Care Service, Centre Hospitalier Universitaire Vaudois, CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
Eur J Clin Microbiol Infect Dis. 2014 Oct;33(10):1861-7. doi: 10.1007/s10096-014-2156-1. Epub 2014 May 24.
The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.
全人源抗脂多糖（LPS）免疫球蛋白M（IgM）单克隆抗体帕诺巴单抗被开发用作治疗O11血清型铜绿假单胞菌感染的辅助免疫疗法。我们评估了帕诺巴单抗治疗医院获得性肺炎的潜在临床疗效。我们对一项多中心IIa期试验（NCT00851435）进行了事后分析，该试验旨在前瞻性评估帕诺巴单抗的安全性和药代动力学。将接受帕诺巴单抗治疗的患者（n = 17），包括13例接受全程治疗（三剂1.2 mg/kg）的患者，与14例未接受该抗体治疗的患者进行比较。总体而言，17例接受帕诺巴单抗治疗的患者病情更严重。他们的平均年龄为72岁[四分位间距（IQR）：64 - 79]，而未接受抗体治疗患者的平均年龄为50岁（IQR：30 - 73）（p = 0.024），急性生理与慢性健康状况评分II（APACHE II）分别为17分（IQR：16 - 22）和15分（IQR：10 - 19）（p = 0.043）。辅助免疫疗法使接受全程三疗程帕诺巴单抗治疗的组临床结局得到改善，缓解率为85%（11/13），而未接受抗体治疗组的缓解率为64%（9/14）（p = 0.048）。Kaplan-Meier生存曲线显示，该组患者临床缓解时间在统计学上显著缩短（8.0天[IQR：7.0 - 11.5]，未接受抗体治疗患者为18.5天[IQR：8 - 30]；p = 0.004）。如果患者接受全程治疗（三剂），帕诺巴单抗辅助免疫疗法可能在更短时间内改善临床结局。这些初步结果表明，针对LPS的被动免疫疗法可能是治疗医院获得性O11铜绿假单胞菌肺炎的一种补充策略。
