Amikacin Liposome Inhalation Suspension in Newly Diagnosed Mycobacterium avium Complex Lung Disease (ARISE): A 6-Month Double-Blind, Active Comparator Trial

Rationale Guidelines recommend Amikacin liposome inhalation suspension (ALIS) for refractory Mycobacterium avium complex lung disease (MACLD) treatment, alongside other antibiotics. Efficacy of ALIS on microbiological endpoints and patient-reported outcomes (PROs) in the newly diagnosed MACLD population is unknown. Objectives ARISE aimed to validate Quality of Life–Bronchiectasis Respiratory Domain (QOL-B RD) and Patient-Reported Outcomes Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS F SF-7a) in patients treated for new/recurrent MACLD. We present treatment outcome results, including microbiological endpoints, PROs, and safety. Methods Adults with noncavitary MACLD were randomized 1:1 to ALIS [590mg] or empty liposome control (comparator), plus azithromycin [250mg] and ethambutol [15mg/kg] once daily for 6 months (M), then 1M off-treatment. Measurements and Main Results Of 99 patients, most had M. intracellulare (43.4%) and/or M. avium (32.3%) infections. Culture conversion with ALIS was achieved by 80.6% by M6 (comparator, 63.9%) and 78.8% by M7 (comparator, 47.1%; nominal P=0.0010). Among patients achieving culture conversion by M6, first negative culture defining conversion occurred at M1 for 74.3% with ALIS (comparator, 46.7%). Mean QOL-B RD score through M7 improved with ALIS vs plateauing with comparator after M3; both arms showed improved PROMIS F SF-7a without between-arm difference. Positive correlations between culture conversion and improved QOL-B RD score were observed with ALIS. No ALIS-related serious adverse events or deaths were reported. Conclusions More patients with newly diagnosed MACLD receiving 6M of ALIS alongside a macrolide-based regimen achieved culture conversion by M6 and M7 numerically more rapidly vs comparator. No new safety signals were identified.