STAGE
Trial question
What is the role of inhaled recombinant human GM-CSF in patients with autoimmune pulmonary alveolar proteinosis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 63
63 patients (27 female, 36 male).
Inclusion criteria: patients with autoimmune pulmonary alveolar proteinosis with a PaO2 < 70 mmHg (or < 75 mmHg in symptomatic patients) on ambient air.
Key exclusion criteria: severe pulmonary alveolar proteinosis (PaO2 < 50 mmHg); lung lavage therapy in the past 6 months; previous GM-CSF or other cytokine therapy; pregnancy.
Interventions
N=33 sargramostim (at a dose of 125 mcg BID for 7 days, every other week for 24 weeks).
N=30 placebo (matching placebo for 7 days, every other week for 24 weeks).
Primary outcome
Mean reduction in alveolar-arterial oxygen gradient at week 25
4.5 mmHg
-0.17 mmHg
4.5 mmHg
3.4 mmHg
2.3 mmHg
1.1 mmHg
0.0 mmHg
-1.1 mmHg
Sargramostim
Placebo
Significant
increase ▲
Significantly greater reduction in mean the alveolar-arterial oxygen gradient at week 25 (4.5 mmHg vs. -0.17 mmHg; ED 5.7, 95% CI 0.89 to 10.51).
Secondary outcomes
Significantly lower reduction in mean mMRC Dyspnea Scale symptom score (0.45 points vs. 0.03 points; ED 0.07, 95% CI 0 to 0.14).
No significant difference in mean change in COPD Assessment Test total score (0.48 points vs. -3.43 points; ED 2, 95% CI 0 to 4).
Safety outcomes
No significant differences in vital capacity, change in walking distance, adverse events, and death.
Conclusion
In patients with autoimmune pulmonary alveolar proteinosis with a PaO2 < 70 mmHg (or < 75 mmHg in symptomatic patients) on ambient air, sargramostim was superior to placebo with respect to mean reduction in the alveolar-arterial oxygen gradient at week 25.
Reference
Ryushi Tazawa, Takahiro Ueda, Mitsuhiro Abe et al. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. N Engl J Med. 2019 Sep 5;381(10):923-932.
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