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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2018

Open Access 01-12-2018 | Research

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis

Authors: Hee-Young Yoon, Jung Jin Hwang, Dong Soon Kim, Jin Woo Song

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

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Abstract

Background

Lymphangioleiomyomatosis is a rare disease caused by unregulated activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but the optimal dose remains unclear.

Methods

We investigated the efficacy and safety of low-dose compared with conventional-dose sirolimus. Clinical data of 39 patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment period, 29.6 months) who received sirolimus were retrospectively reviewed. Low-dose sirolimus was defined as any dose that maintained mean blood trough levels lower than those maintained with conventional doses (5–15 ng/mL).

Results

Fifty-one percent of patients received low-dose therapy. The rate of decline in lung function decreased after treatment in the whole group (forced expiratory volume in 1 s [FEV1], − 0.12 ± 0.47 [before] vs. 0.24 ± 0.48% predicted/month [after], p = 0.027; diffusing capacity for carbon monoxide [DLco], − 0.33 ± 0.61 vs. 0.03 ± 0.26% predicted/month, p = 0.006) compared with before treatment. In the low-dose group, the rate of decline in FEV1 (− 0.08 ± 0.38 [before] vs. 0.19 ± 0.51% predicted/month [after], p = 0.264) and DLco (-0.13 ± 0.62 vs. 0.02 ± 0.28% predicted/month, p = 0.679) showed a numeric trend towards improvement after treatment; however, the conventional-dose group showed significant improvement in FEV1 (− 0.26 ± 0.54 [before] vs. 0.22 ± 0.38 [after] % predicted/month, p = 0.024) and DLco (− 0.55 ± 0.58 vs. 0.04 ± 0.25% predicted/month, p = 0.002) after treatment. Adverse events (AEs) occurred in 89.7% of patients and the most common AEs was hypercholesterolaemia (43.6%), followed by stomatitis (35.9%). The occurrences of AE were similar between the low- and conventional-dose groups (85.0% vs. 94.7%, p = 0.605).

Conclusions

Low-dose sirolimus may stabilise lung function decline in lymphangioleiomyomatosis patients, but its efficacy appears to be inferior to that of conventional-dose sirolimus.
Appendix
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Metadata
Title
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis
Authors
Hee-Young Yoon
Jung Jin Hwang
Dong Soon Kim
Jin Woo Song
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-018-0946-8

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