The drug sirolimus - used to prevent rejection in organ transplant patients - stabilizes lung function in women with lymphangioleiomyomatosis (LAM), and is associated with a reduction in symptoms and improvement in quality of life, finds the MILES study published in the New England Journal of Medicine.

LAM is a rare progressive, lung disease that almost exclusively strikes young women. In LAM smooth muscle cells grow uncontrollably and spread from an unknown source to restricted areas in the body, including the lungs, lymph nodes and vessels and kidneys, limiting the flow of air, blood and lymph. The spread of these cells has led some to categorize LAM as a low grade neoplasm. Until now lung transplantation has been the only hope for patients progressing to respiratory failure.

In the MILES study, led by Frank McCormack from the University of Cincinnati, which involved 13 institutions in the US, Canada and Japan, 89 female patients with LAM were randomized to receive either an initial dose of oral sirolimus at 2 milligrams per day (n=46) or a matched placebo (n=43).

Patients underwent baseline lung function testing, and lung function and exercise outcomes were measured over the course of six visits in the first year. Participants were also given questionnaires to determine how their symptoms changed throughout the course of the study. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV_1 ).

Results showed that in comparison with the placebo group, the sirolimus group showed an improvement from baseline to 12 months in measures of forced vital capacity of 153 ml, or approximately 11% of the mean FEV_1. The sirolimus group additionally showed statistically significant improvements in functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance.

While adverse events were more common with sirolimus, the investigators found that the frequency of serious adverse events did not differ significantly between the groups. The differences between the groups, however, reverted once the drug was stopped.

"These data suggest that there is a need for continued sirolimus therapy, which requires consideration of its long-term toxic effects," wrote Julie Ingelfinger and Jeffrey Brazen in an accompanying editorial. "Even though these data offer women with LAM the prospect of only a long-term treatment rather than a cure, this is a big step forward."

Article: F McCormack, Y Inoue, J Moss, et al. Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis. N Engl J Med 2011; 364:1595-1606.

Reference

J Ingelfinger, J Drazen. Patient Organizations and Research on Rare Diseases. Ibid 1670-1671.