Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia

• DOI: 10.1007/s10096-014-2156-1
• Publication Date: 2014-07-26T15:24:32Z
• Authors: Y.-A. Que; H. Lazar; M. Wolff; B. François; P.-F. Laterre; E. Mercier; J. Garbino; J.-L. Pagani; J.-P. Revelly; E. Mus; A. Perez; M. Tamm; J.-J. Rouby; Q. Lu; J. Chastre; P. Eggimann
• Keywords: Adult; Male; Cross Infection; Antibodies, Monoclonal; Middle Aged; Serogroup; Antibodies, Bacterial; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Immunoglobulin M; Pseudomonas aeruginosa; Pneumonia, Bacterial; Humans; Immunologic Factors; Female; Immunotherapy; Prospective Studies; Aged

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.