Amikacin liposome inhalation suspension in newly diagnosed Mycobacterium avium complex lung disease (ARISE): a 6-month double-blind, active comparator trial

Abstract

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 (590 mg) or empty liposome control (comparator), plus azithromycin (250 mg) and ethambutol (15 mg/kg) once daily for 6 months, then 1 month off treatment.

Results: Of 99 patients, most had Mycobacterium intracellulare (43.4%) and/or M avium (32.3%) infections. Culture conversion with ALIS was achieved by 80.6% by month 6 (comparator, 63.9%) and 78.8% by month 7 (comparator, 47.1%; nominal P = .0010). Among patients achieving culture conversion by month 6, first negative culture defining conversion occurred at month 1 for 74.3% with ALIS (comparator, 46.7%). Mean QOL-B RD score through month 7 improved with ALIS versus plateauing with comparator after month 3; 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 6 months of ALIS alongside a macrolide-based regimen achieved culture conversion by month 6 and month 7 numerically more rapidly versus comparator. No new safety signals were identified.Clinical trial registered with www.clinicaltrials.gov (NCT04677543).

Keywords: Mycobacterium avium complex lung disease; clinical trial; microbiologic outcomes; nontuberculous mycobacterial lung disease; patient-reported outcomes.