Adding inhaled amikacin liposome to first-line therapy improved culture conversion in new MAC lung disease

Design

Phase 3b, randomised, double-blind, placebo-controlled superiority trial (ENCORE)

Population

425 adults with newly diagnosed Mycobacterium avium complex lung disease

Primary outcome

Change in Respiratory Symptom Score from baseline to month 13

Effect

17.77 vs 14.66 points (difference 3.11, P = 0.0299); culture conversion 82.4% vs 55.6%

In ENCORE, a phase 3b double-blind trial, 425 adults newly diagnosed with Mycobacterium avium complex lung disease who had not started antibiotics received azithromycin and ethambutol for 12 months plus either inhaled amikacin liposome 590 mg (213) or placebo (212). The primary endpoint was change in Respiratory Symptom Score from baseline to month 13.

Symptom scores improved more with amikacin liposome (least-squares mean change 17.77 vs 14.66 points; difference 3.11, P = 0.0299), and the difference was 4.80 points at month 15 (nominal P = 0.0015). Culture conversion by month 13 was 82.4% vs 55.6%, and durable conversion at month 15 was 76.2% vs 47.6% (both P below 0.0001). No new safety signals were noted. Median age was 68, and 79.3% of participants were women.

The symptom benefit of about 3 points is modest, and the drug is already approved for refractory disease. The abstract does not give the incidence of respiratory adverse events. In India, access and cost are likely to limit use, and the current guideline regimen remains the standard.

• Confirm the diagnosis by guideline criteria before starting treatment for MAC lung disease.
• Discuss the three-drug first-line regimen in the specialist team; this trial tested a fourth, inhaled agent on top.
• Check availability and cost of inhaled amikacin liposome before planning.
• Monitor for cough, dysphonia and hypersensitivity if an inhaled agent is added.
• Do not read culture conversion as clinical cure; follow symptoms and imaging.

Why it matters

It tests a drug approved for refractory disease in the setting where a better first-line option is most needed.

Don't overread it

The primary symptom endpoint difference was modest and culture conversion is a surrogate; sponsor-funded trial data are not yet in guidelines.

The statistics, in plain English

A culture conversion of 82.4% vs 55.6% is a gap of about 27 percentage points, which is large and clearly beyond chance. The symptom score difference of 3.11 points was statistically significant but small, so it is hard to say how much a patient would notice.

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