Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis
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 investi...
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doaj-da3eae0db5ad493da6eb00e3feaf4b602020-11-25T02:17:19ZengBMCOrphanet Journal of Rare Diseases1750-11722018-11-011311810.1186/s13023-018-0946-8Efficacy and safety of low-dose Sirolimus in LymphangioleiomyomatosisHee-Young Yoon0Jung Jin Hwang1Dong Soon Kim2Jin Woo Song3Departments of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartment of Convergence Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartments of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of MedicineDepartments of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13023-018-0946-8LymphangioleiomyomatosisSirolimusLow doseRespiratory function testsTreatment outcome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hee-Young Yoon Jung Jin Hwang Dong Soon Kim Jin Woo Song |
spellingShingle |
Hee-Young Yoon Jung Jin Hwang Dong Soon Kim Jin Woo Song Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis Orphanet Journal of Rare Diseases Lymphangioleiomyomatosis Sirolimus Low dose Respiratory function tests Treatment outcome |
author_facet |
Hee-Young Yoon Jung Jin Hwang Dong Soon Kim Jin Woo Song |
author_sort |
Hee-Young Yoon |
title |
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis |
title_short |
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis |
title_full |
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis |
title_fullStr |
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis |
title_full_unstemmed |
Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis |
title_sort |
efficacy and safety of low-dose sirolimus in lymphangioleiomyomatosis |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2018-11-01 |
description |
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. |
topic |
Lymphangioleiomyomatosis Sirolimus Low dose Respiratory function tests Treatment outcome |
url |
http://link.springer.com/article/10.1186/s13023-018-0946-8 |
work_keys_str_mv |
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