Update in Interstitial Lung Disease (ILD) Clinical Trials
Results of the Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) Trial were presented at this year’s American Thoracic Society International Meeting.
The MILES trial randomized 89 patients with lymphangioleiomyomatosis (LAM) (mean FEV1 48 ± 13.8%) to receive the mTOR inhibitor sirolimus (Rapamycin, N=46) or placebo (N=43) in a 12-month, double-blind, placebo-controlled study followed by a 12-month observation period during which no subject received study medications. The primary endpoint was the rate of change in FEV1 (the FEV1 slope). Secondary endpoints included change in forced vital capacity (FVC), lung volumes, and Dlco, as well as 6-min hall walk distance, serum VEGF-D levels, and quality of life measures.
Investigators found that, over 12 months, FEV1 decreased significantly in subjects receiving placebo compared with those receiving sirolimus, in whom FEV1 remained essentially stable. Similar findings were observed for the FVC, and subjects receiving sirolimus had a significant decrease in serum VEGF-D levels compared with those receiving placebo. There were no significant differences between groups with respect to other secondary endpoints. Over the course of the subsequent 12-month observation period, FEV1 declined by similar amounts in both groups, suggesting that withdrawal of sirolimus did not enhance FEV1 decline. Serum VEGF-D levels remained lower during the observation period in subjects receiving sirolimus. There were significantly more adverse events in the sirolimus group, with serious adverse cardiac events (pericarditis, atrial dysrhythmia, and tachycardia) only occurring in the sirolimus group.
The authors conclude that sirolimus therapy may be beneficial for select patients with moderately severe LAM-related lung disease, although future studies are needed to evaluate optimal dosing and duration of therapy. Study results have been published in the New England Journal of Medicine (McCormack et al. 2011;364[17]:1595).
Dr. Eric S. White, FCCP
Steering Committee Member
