Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a six month phase II randomized study with 24 months of follow-up

Abstract

Background: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited. Methods: In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed.

Nebulised sargramostim in pulmonary alveolar proteinosis

“…21 oxygen gradient, but with significant improvement in diffusion gradient, total lung capacity and symptoms (SGRQ). 22 In our case series, a statistically significant result was observed for the change in FVC (predicted percent) at 6 months compared to baseline (P = .036). However, this was not sustained at 12 months.…”

“…Pivotal clinical data of GM‐CSF use in alveolar proteinosis has been established by the Tazawa, Trapnell and Tian research groups 17–22 . The first phase II trial of nebulised sargramostim was published in 2010 18 .…”

“…Trapnell et al reported on 91 patients treated with inhaled GM‐CSF, finding significant improvement in alveolar arterial oxygen gradient and measure of health‐related quality of life (St George's Respiratory Questionnaire; SGRQ) with no difference in adverse events between active and placebo‐treated patients 21 . Tian et al reported on treatment of 19 patients observing no change in arterial‐alveolar oxygen gradient, but with significant improvement in diffusion gradient, total lung capacity and symptoms (SGRQ) 22 . In our case series, a statistically significant result was observed for the change in FVC (predicted percent) at 6 months compared to baseline ( P = .036).…”

“…Recently, further recombinant GM-CSF analogues, including molgramostim and HUABEI JIMUXIN, have been developed and evaluated in clinical trial settings. 21,22 We aimed to describe the patient characteristics and responses to nebulised GM-CSF for PAP in an Australian health care setting.…”

Update on Diagnosis and Treatment of Adult Pulmonary Alveolar Proteinosis

“… 35 In another six-month Phase II randomized study involving 36 autoimmune PAP patients, inhaled GM-CSF (molgramostim) for six months had no impact on the alveolar-arterial (A-a) oxygen gradient in patients who had mild to moderate pulmonary alveolar proteinosis. 36 Health-related quality of life measures did improve after three months of treatment, and there was a marginal improvement in terms of total lung capacity and diffusion capacity. In the recently concluded largest randomized trial of 138 patients, a continuous regimen of 300 mcg of molgramostim, in comparison with an intermittent regimen and placebo, demonstrated statistically significant improvement in pulmonary gas transfer, clinical parameters (including biomarkers and ground glass on CT scan) and functional health status compared to placebo, with similar rates of adverse events.…”