Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Aug 20;14(1):206.
doi: 10.1186/s13023-019-1178-2.

Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis

Siqi Hu  1   2   3 , Xiuxiu Wu  1   4 , Wenshuai Xu  1 , Xinlun Tian  1   5 , Yanli Yang  1   5 , Shao-Ting Wang  1   5 , Song Liu  5   6 , Xingxiang Xu  2 , Kai-Feng Xu  7   8
Affiliations

Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis

Siqi Hu et al. Orphanet J Rare Dis. .

Abstract

Background: Sirolimus has been confirmed to be effective for lymphangioleiomyomatosis (LAM), a rare multisystem neoplastic disease in women. The long-term effects of sirolimus treatment for LAM, however, are largely unknown. We aimed to analyze the long-term efficacy and safety of sirolimus therapy for LAM with 4-year follow-up.

Methods: In total, 142 sporadic LAM patients who took sirolimus for 1-4 years were retrospectively enrolled for this analysis. The variables used for analysis included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), St. George's Respiratory Questionnaires (SGRQ) and serum vascular endothelial growth factor-D (VEGF-D) levels before and after the initiation of sirolimus therapy. The rates of change (slope) in those variables were calculated, and adverse events were also analyzed.

Results: In total, 122, 83, 60 and 32 patients out of 142 were followed for 1, 2, 3 and 4 years respectively. Sirolimus treatment improved the change rate in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) compared with the data before treatment (FEV1, - 10 ± 15 vs. - 178 ± 36 ml/y, P < 0.001 and FVC, 54 ± 22 vs.-72 ± 68 ml/y, P < 0.05). In comparison to the baseline measurements, significant improvements were observed in FEV1 at the first year; FVC at 1-2 years; arterial oxygen levels, 6MWD, and SGRQ at 1-3 years; and VEGF-D at 1-4 years. Overall, all variables stabilized or improved during the 4 years of observation. Adverse events related to sirolimus were mild.

Conclusion: Sirolimus therapy is effective at improving or stabilizing pulmonary function, oxygen levels, exercise capacity, and quality of life in patients with LAM for up to 4 years. VEGF-D is maintained at a lower level for 4 years after treatment. Adverse events related to sirolimus were mild.

Keywords: Lymphangioleiomyomatosis; Pulmonary function; Sirolimus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Johnson SR, Taveira-DaSilva AM, Moss J. Lymphangioleiomyomatosis. Clin Chest Med. 2016;37(3):389–403. doi: 10.1016/j.ccm.2016.04.002. - DOI - PubMed
    1. Harari S, Torre O, Cassandro R, Moss J. The changing face of a rare disease: lymphangioleiomyomatosis. Eur Respir J. 2015;46(5):1471–1485. doi: 10.1183/13993003.00412-2015. - DOI - PubMed
    1. Henske EP, McCormack FX. Lymphangioleiomyomatosis - a wolf in sheep’s clothing. J Clin Invest. 2012;122(11):3807–3816. doi: 10.1172/JCI58709. - DOI - PMC - PubMed
    1. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364(17):1595–1606. doi: 10.1056/NEJMoa1100391. - DOI - PMC - PubMed
    1. McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG, et al. Official American Thoracic Society/Japanese respiratory society clinical practice guidelines: Lymphangioleiomyomatosis diagnosis and management. Am J Respir Crit Care Med. 2016;194(6):748–761. doi: 10.1164/rccm.201607-1384ST. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources