- Design
- Phase 3b, randomised, double-blind, placebo-controlled trial
- Population
- 425 adults with newly diagnosed MAC lung disease
- Primary outcome
- Change in respiratory symptom score at month 13
- Effect
- Difference 3.1 points; culture conversion 82.4% vs 55.6%
ENCORE, published in AJRCCM on 30 September 2026, was a phase 3b double-blind trial in 425 adults newly diagnosed with Mycobacterium avium complex lung disease who had not started antibiotics. Median age was 68 and four in five were women. All received azithromycin 250 mg and ethambutol 15 mg/kg daily for 12 months, plus amikacin liposome inhalation suspension 590 mg or placebo.
Respiratory symptom scores improved more with inhaled amikacin at month 13 (difference 3.1 points, P = 0.03) and month 15 (4.8 points). Culture conversion by month 13 was 82.4% against 55.6%, and durable conversion at month 15 was 76.2% against 47.6% (both P below 0.0001). No new safety signals were reported.
Current guidelines start with oral three-drug therapy and reserve inhaled amikacin for refractory disease, which is also where it is licensed. ENCORE is the first randomised evidence for adding it from the start. The symptom gain was modest; the microbiological gain was large. Guidelines and licences have not yet changed, and cost and access will weigh heavily.
- Consider discussing upfront inhaled amikacin with patients newly diagnosed with MAC lung disease, recognising it is beyond the current licence.
- Keep azithromycin and ethambutol as the backbone in all regimens.
- Monitor for hearing, balance and renal effects with any amikacin formulation.
- Follow guideline-recommended treatment until guidance is updated.
- Check local availability and cost; inhaled liposomal amikacin is expensive.
Why it matters
Front-line MAC therapy has poor conversion rates, and this is a randomised way to improve them early.
Don't overread it
The licence and current guidelines still reserve it for refractory disease; symptom benefit was small.
The statistics, in plain English
A 27-point gain in culture conversion is large and very unlikely to be chance. The 3-point symptom difference was statistically significant, but its clinical importance is less certain.
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