David E Griffith1, Rachel Thomson2, Patrick A Flume3, Timothy R Aksamit4, Stephen K Field5, Doreen J Addrizzo-Harris6, Kozo Morimoto7, Wouter Hoefsloot8, Kevin C Mange9, Dayton W Yuen9, Monika Ciesielska9, Richard J Wallace10, Jakko van Ingen11, Barbara A Brown-Elliott10, Chris Coulter12, Kevin L Winthrop13. 1. Pulmonary Infectious Disease Section, The University of Texas Health Science Center at Tyler, Tyler, TX. Electronic address: griffithd@njhealth.org. 2. Gallipoli Medical Research Institute, University of Queensland, Brisbane, QLD, Australia. 3. Departments of Medicine and Pediatrics, Medical University of South Carolina, Charleston, SC. 4. Pulmonary Disease and Critical Care Medicine, Mayo Clinic, Rochester, MN. 5. Division of Respirology and TB Services, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 6. Division of Pulmonary, Critical Care and Sleep Medicine, New York University Grossman School of Medicine, New York, NY. 7. Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan. 8. Department of Pulmonary Diseases, Radboud University Medical Center-Dekkerswald, Nijmegen, the Netherlands. 9. Insmed Incorporated, Bridgewater, NJ. 10. Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX. 11. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands. 12. Queensland Mycobacterium Reference Laboratory, Pathology Queensland, Brisbane, QLD, Australia. 13. Division of Infectious Disease, Oregon Health and Science University School of Medicine, Portland, OR.
Abstract
BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.
BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.
Authors: Theodore K Marras; Mariam Hassan; Kevin C Mange; Monika Ciesielska; Shilpa Dhar Murthy; Zhanna Jumadilova; Anjan Chatterjee Journal: ERJ Open Res Date: 2022-07-11
Authors: Adam J Plaunt; Tam L Nguyen; Michel R Corboz; Vladimir S Malinin; David C Cipolla Journal: Pharmaceutics Date: 2022-01-27 Impact factor: 6.321