Efficacy and Safety of TOBI Podhaler in Pseudomonas Aeruginosa-Infected Bronchiectasis Patients: Ibest Study

ORIGINAL ARTICLE BRONCHIECTASIS

Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study

Michael R. Loebinger1,2, Eva Polverino3, James D. Chalmers4, Harm A.W.M. Tiddens5,6, Herman Goossens7, Michael Tunney8, Felix C. Ringshausen 9, Adam T. Hill10, Rashidkhan Pathan11, Gerhild Angyalosi12, Francesco Blasi 13,14, Stuart J. Elborn2,15,16 and Charles S. Haworth17,18 on behalf of the iBEST-1 Trial Team

Affiliations: 1Host Defence Unit, Royal Brompton Hospital and Harefield NHS Foundation Trust, London, UK. 2Imperial College London, London, UK. 3Respiratory Disease Department, Vall d’ Hebron University Hospital – VHIR, Barcelona, Spain. 4Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. 5Dept of Paediatric Pulmonology and Allergology, Erasmus Medical Centre Sophia Children’s Hospital, Rotterdam, The Netherlands. 6Dept of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. 7Dept of Clinical Microbiology, University Hospital Antwerp, Antwerp, Belgium. 8Halo Research Group, School of Pharmacy, Queen’s University Belfast, Belfast, UK. 9Dept of Respiratory Medicine, Hannover Medical School, and Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany. 10Dept of Respiratory Medicine, Royal Infirmary of Edinburgh, and University of Edinburgh, Edinburgh, UK. 11Novartis Healthcare Private Limited, Hyderabad, India. 12Novartis Pharma AG, Basel, Switzerland. 13Internal Medicine Dept, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. 14Dept of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. 15Halo Research Group, Centre for Experimental Medicine, Queen’s University Belfast, Belfast, UK. 16Imperial College and Royal Brompton Hospital and Harefield NHS Foundation Trust, London, UK. 17Cambridge Centre for Lung Infection, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK. 18Dept of Medicine, University of Cambridge, Cambridge, UK.

Correspondence: Michael R. Loebinger, Royal Brompton and Harefield NHS Foundation Trust, Sydney St, London, SW3 6NP, UK. E-mail: [email protected]

@ERSpublications Inhaled dry powder tobramycin (TOBI Podhaler) significantly reduced Pseudomonas aeruginosa sputum density and was well tolerated in patients with bronchiectasis https://bit.ly/3hsRQw9

Cite this article as: Loebinger MR, Polverino E, Chalmers JD, et al. Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study. Eur Respir J 2021; 57: 2001451 [https://doi.org/10.1183/13993003.01451-2020].

This single-page version can be shared freely online.

ABSTRACT The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis. This is a phase II, double-blind, randomised study in bronchiectasis patients aged ⩾18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively and were followed up for 8 weeks. Overall, 107 patients were randomised to cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the P. aeruginosa sputum density from baseline to day 29 versus placebo in a dose-

Link to published version: https://doi.org/10.1183/13993003.01451-2020 Eur Respir J 2021; 57: 2001451 BRONCHIECTASIS | M.R. LOEBINGER ET AL.

dependent manner (p⩽0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous TIP and 42.9% on cyclical TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of bronchiectasis was the most frequent (37.4%) adverse event. Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to adverse events. Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the P. aeruginosa sputum density in patients with bronchiectasis and chronic P. aeruginosa infection.

Link to published version: https://doi.org/10.1183/13993003.01451-2020 2