RT Journal Article SR Electronic T1 Changes in respiratory symptoms during 48 weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2000110 DO 10.1183/13993003.00110-2020 A1 James D Chalmers A1 David Cipolla A1 Bruce Thompson A1 Angela M Davis A1 Anne O'Donnell A1 Gregory Tino A1 Igor Gonda A1 Charles Haworth A1 Juergen Froehlich YR 2020 UL http://erj.ersjournals.com/content/early/2020/05/25/13993003.00110-2020.abstract AB Introduction It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48-weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment.Methods A post-hoc analysis of 2 identical randomised trials of ARD-3150 (ORBIT-3 and -4) administered 28-days on and 28 days off in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The quality of life bronchiectasis respiratory symptom scale (QOL-B-RSS), which has a 1-week recall period, was administered every 28-days. We examined whether respiratory symptoms improved during on-treatment periods and the relationship of changes in QOL-B-RSS to changes in bacterial load using a mixed model repeated measures approach.Results ARD-3150 treatment resulted in a significant improvement in respiratory symptoms during the on-treatment periods with concordant results between ORBIT-3 (estimate 1.4 points, standard error (se) 0.49, p=0.004) and ORBIT-4 (estimate 1.1 point, SE0.41, p=0.006). The proportion of patients achieving a symptom improvement above the minimum clinically important difference was higher with ARD-3150 compared to placebo during on-treatment cycles (p=0.024). Changes in respiratory symptoms were correlated with changes in bacterial load in the treatment group (r=−0.89, p<0.0001). Individual estimates for decrements in the QOL-B RSS during exacerbation were −9.4 points (se 0.91) in ORBIT-3 and −10.8 points (0.74) in ORBIT-4 (both p<0.0001).Conclusion Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Chalmers reports grants and personal fees from Astrazeneca, grants and personal fees from Glaxosmithkline, personal fees from Chiesi, grants from Gilead, grants and personal fees from Grifols, grants and personal fees from Insmed, grants and personal fees from Boehringer Ingelheim, outside the submitted work;.Conflict of interest: Dr. Cipolla reports In addition, Dr. Cipolla has a patent US 10,420,765 issued, a patent US 9,987,227 issued, a patent US 9,968,555 issued, a patent US 9,844,548 issued, a patent US 9,545,401 issued, a patent US 9,259,424 issued, a patent US 9,078,897 issued, a patent US 9,028,864 issued, a patent US 8,414,915 issued, a patent US 8,268,347 issued, a patent US 8,119,156 issued, and a patent US 8,071,127 issued.Conflict of interest: Dr. Thompson reports personal fees from Aradigm, during the conduct of the study;.Conflict of interest: Dr. Davis reports personal fees from Grifols, during the conduct of the study;.Conflict of interest: Dr. O'Donnell reports personal fees from Aradigm, during the conduct of the study;.Conflict of interest: Dr. Tino has nothing to disclose.Conflict of interest: Dr. Gonda reports personal fees from Aradigm Corporation, during the conduct of the study; other from Aradigm Corporation, outside the submitted work; In addition, Dr. Gonda has a patent Aradigm Corporation licensed, and a patent Aradigm Corporation licensed.Conflict of interest: Dr. Haworth reports personal fees from Aradigm, personal fees from Grifols, during the conduct of the study; personal fees from Zambon / Profile , personal fees from Chiesi, grants and personal fees from Insmed, personal fees from Gilead, personal fees from GSK, grants from Novartis, grants and personal fees from TEVA, outside the submitted work;.Conflict of interest: Dr. Froehlich reports personal fees from Aradigm, during the conduct of the study;.